HIV protease inhibiting compounds

ABSTRACT

A compound of the formula 
     
       
         
         
             
             
         
       
     
     is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

This application claims priority to the provisional application Ser. No.60/529,121 filed on Dec. 11, 2003.

TECHNICAL FIELD

The present invention relates to novel compounds and a composition and amethod for inhibiting human immunodeficiency virus (HIV) protease, acomposition and method for inhibiting or treating an HIV infection,processes for making the compounds and synthetic intermediates employedin the processes.

BACKGROUND OF THE INVENTION

The genome of the human immunodeficiency virus (HIV) encodes a proteasethat is responsible for the proteolytic processing of one or morepolyprotein precursors such as the pol and gag gene products. HIVprotease processes the gag precursor into core proteins and alsoprocesses the pol precursor into reverse transcriptase and protease.

The correct processing of the precursor polyproteins by HIV protease isnecessary for the assembly of infectious virions. Therefore, inhibitionof HIV protease provides a useful target for development of therapeuticagents for treatment of HIV infection.

In recent years, inhibitors of HIV protease have become an importantclass of therapeutic agents for inhibition and treatment of HIVinfection in humans. HIV protease inhibitors are especially effectivewhen administered in combination with other classes of HIV therapeuticagents, especially inhibitors of HIV reverse transcriptase, in“cocktails” of HIV therapeutic agents.

At the present time, the HIV protease inhibitors saquinavir, ritonavir,indinavir, nelfinavir, amprenavir, lopinavir/ritonavir, fosamprenavir,and atazanavir have been approved in the U.S. for treatment of HIVinfection. There is a continuing need for improved HIV proteaseinhibitors that are very potent, that have reduced side-effects and thatare effective against resistant strains of HIV.

SUMMARY OF THE INVENTION

The present invention provides a compound of formula (I)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein:

A is R₅C(O)—, R₆SO₂—,

X is O, S or NH; Y is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, haloalkyl,hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₅ is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -OalkylSO₂alkyl, —O-heterocycle, -alkyl-O-aryl or—O-alkyl-heteroaryl; wherein the heterocycle, aryl or heteroaryl moietyof —O-heterocycle, -alkyl-O-aryl and —O-alkyl-heteroaryl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂;R₆ is aryl or heteroaryl; wherein each R₆ is substituted with 0 or 1substituent selected from the group consisting of —C(H)═NOH,—C(alkyl)=NOH, —C(H)═NO(alkyl), —C(alkyl)=NO(alkyl), —C(H)═NO(arylalkyl)and —C(alkyl)=NO(arylalkyl);R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂;

R₈ is —C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b),

R_(8a) and R_(8b) are, at each occurrence, independently selected fromthe group consisting of alkyl, arylalkyl and heteroarylalkyl; whereineach R_(8a) and R_(8b) is independently substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of alkyl,nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl;R₉ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₉ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(9a);R_(9a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(9a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₀ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₀ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(10a);R_(10a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(10a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₁ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₁ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(E), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b),—C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b),—C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(11a);R_(11a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(11a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₂ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl orcycloalkenylalkyl; wherein each R₁₂ is substituted with 0, 1 or 2substituents independently selected from the group consisting ofhydroxy, alkoxy cyano, nitro and halo;R₁₃ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle; wherein each R₁₃ is substituted with 0, 1, 2or 3 substituents independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(a))NR_(a)R_(b), —N(ROC(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(13a);R_(13a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(13a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or 2.

The present invention also provides the processes of making a compoundof the present invention and intermediates employed in the processes.

The present invention further provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of the present invention, or a pharmaceuticallyacceptable salt form, stereoisomer, ester, salt of an ester, prodrug,salt of a prodrug, or combination thereof, and a pharmaceuticallyacceptable carrier.

The present invention yet further provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of the present invention, or a pharmaceuticallyacceptable salt form, stereoisomer, ester, salt of an ester, prodrug,salt of a prodrug, or combination thereof, and one, two, three, four,five or six agents selected from the group consisting of a second HIVprotease inhibitor, a HIV reverse transcriptase inhibitor, an HIVentry/fusion inhibitor, an HIV integrase inhibitor and an HIVbudding/maturation inhibitor, and a pharmaceutically acceptable carrier.

The present invention still further provides a method of inhibiting thereplication of an HIV virus comprising contacting said virus with atherapeutically effective amount of a compound or combination ofcompounds of the present invention, or a pharmaceutically acceptablesalt form, stereoisomer, ester, salt of an ester, prodrug, salt of aprodrug, or combination thereof.

The present invention still further provides a method of inhibiting thereplication of an HIV virus comprising contacting said virus with anyone of the pharmaceutical composition of the present invention.

The present invention still further provides a method of inhibiting anHIV protease comprising contacting said HIV protease with atherapeutically effective amount of a compound or combination ofcompounds of the present invention, or a pharmaceutically acceptablesalt form, stereoisomer, ester, salt of an ester, prodrug, salt of aprodrug, or combination thereof.

The present invention still further provides a method of inhibiting anHIV protease comprising contacting said HIV protease with any one of thepharmaceutical composition of the present invention.

The present invention also provides a method of treating or preventingan HIV infection comprising administering to a patient in need of suchtreatment a therapeutically effective amount of a compound orcombination of compounds of the present invention, or a pharmaceuticallyacceptable salt form, stereoisomer, ester, salt of an ester, prodrug,salt of a prodrug, or combination thereof.

The present invention also provides a method of treating or preventingan HIV infection comprising administering to a patient in need of suchtreatment any one of the pharmaceutical composition of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

As used in the present specification the following terms have themeanings indicated:

As used herein, the singular forms “a”, “an”, and “the” may includeplural reference unless the context clearly dictates otherwise.

The term “activated carboxylic acid group” as used herein refers to acidhalides such as acid chlorides and also refers to activated esterderivatives including, but not limited to, formic and acetic acidderived anhydrides, anhydrides derived from alkoxycarbonyl halides suchas isobutyloxycarbonylchloride and the like, anhydrides derived fromreaction of the carboxylic acid with N,N′-carbonyldiimidazole and thelike, N-hydroxysuccinimide derived esters, N-hydroxyphthalimide derivedesters, N-hydroxybenzotriazole derived esters,N-hydroxy-5-norbornene-2,3-dicarboximide derived esters,2,4,5-trichlorophenol derived esters, p-nitrophenol derived esters,phenol derived esters, pentachlorophenol derived esters,8-hydroxyquinoline derived esters and the like.

The term “alkanoyl” as used herein refers to an alkyl group attached tothe parent molecular moiety through a carbonyl group. Examples ofalkanoyl include methylcarbonyl, ethylcarbonyl, tert-butylcarbonyl andthe like.

The term “alkyl,” as used herein, refers to a group derived from astraight or branched chain saturated hydrocarbon containing 1, 2, 3, 4,5, 6, 7, 8, 9 or 10 carbon atoms. Examples of alkyl groups includebutyl, methyl, 1-methylpropyl, 2-methylbutyl, tert-butyl, isopropyl, andthe like.

The term “alkylamino” as used herein refers to —N(H)R⁹⁰ wherein R⁹⁰ isalkyl.

The term “alkylaminocarbonyl” as used herein refers to an alkylaminogroup attached to the parent molecular moiety through a carbonyl group.

The term “alkenyl,” as used herein, refers to a straight or branchedchain group of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms containing atleast one carbon-carbon double bond. Examples of alkenyl groups includealkyl, propenyl, 3-methyl-2-butenyl, and the like.

The term “alkynyl,” as used herein, refers to a straight or branchedchain hydrocarbon of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atomscontaining at least one carbon-carbon triple bond. Examples of alkynylgroups include ethynyl, 2-methyl-3-butynyl, 3-pentynyl, and the like.

The term “alkoxy,” as used herein, refers to an alkyl group attached tothe parent molecular moiety through an oxygen atom. Examples of alkoxygroups include tert-butoxy, methoxy, isopropoxy, and the like.

The term “alkoxyalkyl,” as used herein, refers to an alkyl groupsubstituted by at least one alkoxy group.

The term “alkoxycarbonyl,” as used herein, refers to an alkoxy groupattached to the parent molecular moiety through a carbonyl group.Examples of alkoxycarbonyl groups include tert-butoxycarbonyl,ethoxycarbonyl, methoxycarbonyl, and the like.

The term “amino” as used herein, refers to —NH₂.

The term “aminoalkyl” as used herein, refers to an amino group appendedto the parent molecular moiety through an alkyl group as defined herein.

The term “aryl” as used herein, refers to a phenyl group, or a bicyclicor tricyclic hydrocarbon fused ring systems wherein one or more of therings is a phenyl group. Bicyclic fused ring systems have a phenyl groupfused to a monocyclic cycloalkenyl group, as defined herein, amonocyclic cycloalkyl group, as defined herein, or another phenyl group.Tricyclic fused ring systems are exemplified by a bicyclic fused ringsystem fused to a monocyclic cycloalkenyl group, as defined herein, amonocyclic cycloalkyl group, as defined herein, or another phenyl group.Examples of aryl groups include anthracenyl, azulenyl, fluorenyl,indanyl, indenyl, naphthyl, phenyl, tetrahydronaphthyl, and the like.The aryl groups of the present invention can be connected to the parentmolecular moiety through any substitutable carbon atom of the group. Thearyl groups of the present invention can be substituted orunsubstituted.

The term “arylalkyl,” as used herein, refers to an aryl group attachedto the parent molecular moiety through an alkyl group.

The term “carbonyl” as used herein, refers to —C(═O).

The term “cyano,” as used herein, refers to —CN.

The term “cyanoalkyl,” as used herein, refers to a cyano group attachedto the parent molecular moiety through an alkyl group.

The term “cycloalkenyl,” as used herein, refers to a non-aromatic,partially unsaturated, monocyclic, bicyclic or tricyclic ring system,having three to fourteen carbon atoms and zero heteroatom. Examples ofcycloalkenyl groups include cyclohexenyl, octahydronaphthalenyl,norbornylenyl, and the like. The cycloalkenyl groups of the presentinvention can be unsubstituted or substituted.

The term “cycloalkenylalkyl,” as used herein, refers to a cycloalkenylgroup attached to the parent molecular moiety through an alkyl group.

The term “cycloalkyl,” as used herein, refers to a saturated monocyclic,bicyclic, or tricyclic hydrocarbon ring system having three to fourteencarbon atoms and zero heteroatom. Examples of cycloalkyl groups includecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,bicyclo[3.1.1]heptyl, 6,6-dimethylbicyclo[3.1.1]heptyl, adamantyl, andthe like. The cycloalkyl groups of the present invention can beunsubstituted or substituted.

The term “cycloalkylalkyl,” as used herein, refers to a cycloalkyl groupattached to the parent molecular moiety through an alkyl group.

The term “dialkylamino” as used herein refers to —NR⁹⁰R⁹¹, wherein R⁹⁰and R⁹¹ are alkyls.

The term “dialkylaminocarbonyl” as used herein refers to a dialkylaminogroup as defined herein, appended to the parent molecular moiety througha carbonyl group.

The term “formyl”, as used herein, refers to a —C(O)H group.

The term “formylalkyl” as used herein, refers to a formyl group appendedto the parent molecular moiety through an alkyl group.

The terms “halo,” and “halogen,” as used herein, refer to F, Cl, Br, andI.

The term “haloalkenyl,” as used herein, refers to an alkenyl groupsubstituted by one, two, three, or four halogen atoms.

The term “haloalkoxy” as used herein, refers to a haloalkyl groupattached to the parent molecular moiety through an oxygen atom.

The term “haloalkoxyalkyl” as used herein, refers to a haloalkoxy groupattached to the parent molecular moiety through an alkyl group, asdefined herein.

The term “haloalkyl,” as used herein, refers to an alkyl groupsubstituted by one, two, three, or four halogen atoms.

The term “haloalkynyl,” as used herein, refers to an alkynyl groupsubstituted by one, two, three, or four halogen atoms.

The term “heteroaryl,” as used herein, refers to an aromatic five- orsix-membered ring where at least one atom is selected from the groupconsisting of N, O, and S, and the remaining atoms are carbon. The term“heteroaryl” also includes bicyclic systems where a heteroaryl ring isfused to a phenyl group, a monocyclic cycloalkyl group, as definedherein, a heterocycle group, as defined herein, or an additionalheteroaryl group. The term “heteroaryl” also includes tricyclic systemswhere a bicyclic system is fused to a phenyl group, a monocycliccycloalkyl group, as defined herein, a heterocycle group, as definedherein, or an additional heteroaryl group. The heteroaryl groups areconnected to the parent molecular moiety through any substitutablecarbon or nitrogen atom in the groups. Examples of heteroaryl groupsinclude benzothienyl, benzoxazolyl, benzimidazolyl, benzoxadiazolyl,benzofuranyl, dihydrobenzothiazolyl, furanyl (furyl), imidazolyl,3H-[4,5-b]pyridinyl, indazolyl, indolyl, isoindolyl, isoxazolyl,isoquinolinyl, isothiazolyl, oxadiazolyl, oxazolyl, thiazolyl,thienopyridinyl, thienyl, triazolyl, thiadiazolyl, tetrazolyl,pyridoimidazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,pyrazolyl, pyrrolyl, quinolinyl, tetrahydroquinolinyl, triazinyl, andthe like. The heteroaryl groups of the present invention can besubstituted or unsubstituted. In addition, the nitrogen heteroatoms canbe optionally quaternized or oxidized to the N-oxide. Also, the nitrogencontaining rings can be optionally N-protected.

The term “heteroarylalkyl”, as used herein, refers to refers to aheteroaryl group attached to the parent molecular moiety through analkyl group.

The term “heterocycle,” as used herein, refers to cyclic, non-aromatic,saturated or partially unsaturated, three, four, five-, six-, orseven-membered rings containing at least one atom selected from thegroup consisting of oxygen, nitrogen, and sulfur. The term “heterocycle”also includes bicyclic systems where a heterocycle ring is fused to aphenyl group, a monocyclic cycloalkenyl group, as defined herein, amonocyclic cycloalkyl group, as defined herein, or an additionalmonocyclic heterocycle group. The term “heterocycle” also includestricyclic systems where a bicyclic system is fused to a phenyl group, amonocyclic cycloalkenyl group, as defined herein, a monocycliccycloalkyl group, as defined herein, or an additional monocyclicheterocycle group. The heterocycle groups of the invention are connectedto the parent molecular moiety through any substitutable carbon ornitrogen atom in the group. Examples of heterocycle groups includebenzoxazinyl, 1,3-benzodioxol, dihydroindolyl, dihydropyridinyl,1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, tetrahydrofuranyl,hexahydrofurofuranyl, hexahydrofuropyranyl, isoindolinyl, morpholinyl,piperazinyl, pyrrolidinyl, tetrahydropyridinyl, piperidinyl,thiomorpholinyl, tetrahydropyranyl, and the like. The heterocycle groupsof the present invention can be substituted or substituted. In addition,the nitrogen heteroatoms can be optionally quaternized or oxidized tothe N-oxide. Also, the nitrogen containing heterocyclic rings can beoptionally N-protected.

The term “heterocyclealkyl”, as used herein, refers to refers to aheterocycle group attached to the parent molecular moiety through analkyl group.

The term “hydroxy” or “hydroxyl” as used herein, refers to —OH.

The term “hydroxyalkyl,” as used herein, refers to an alkyl group assubstituted by at least one hydroxy group.

The term “nitro,” as used herein, refers to —NO₂.

The term “nitroalkyl,” as used herein, refers to an alkyl groupsubstituted by at least one nitro group.

The term “oxo,” as used herein, refers to ═O.

The term “thioalkoxy”, as used herein, refers to an alkyl group asdefined herein, appended to the parent molecular moiety through a sulfuratom.

The term “thioalkoxyalkyl”, as used herein, refers to an thioalkoxygroup as defined herein, appended to the parent molecular moiety througha alkyl group.

It is understood that each of the terms alkanoyl, alkenyl, alkoxy,alkoxyalkyl, alkoxycarbonyl, alkyl, alkylamino, alkylaminocarbonyl,alkynyl, aminoalkyl, aryl, arylalkyl, cyanoalkyl, cycloalkenyl,cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, dialkylamino,dialkylaminocarbonyl, formylalkyl, haloalkenyl, haloalkoxy,haloalkoxyalkyl, haloalkynyl, haloalkyl, heteroaryl, heteroarylalkyl,heterocycle, heterocyclealkyl, hydroxyalkyl, nitroalkyl, thioalkoxy andthioalkoxyalkyl may be unsubstituted or substituted.

In a first embodiment, the present invention provides a compound offormula (I),

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein:

A is R₅C(O)—, R₆SO₂—,

X is O, S or NH; Y is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —NR_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₅ is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -OalkylSO₂alkyl, —O-heterocycle, -alkyl-O-aryl or—O-alkyl-heteroaryl; wherein the heterocycle, aryl or heteroaryl moietyof —O-heterocycle, -alkyl-O-aryl and —O-alkyl-heteroaryl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂;R₆ is aryl or heteroaryl; wherein each R₆ is substituted with 0 or 1substituent selected from the group consisting of —C(H)═NOH,—C(alkyl)=NOH, —C(H)═NO(alkyl), —C(alkyl)=NO(alkyl), —C(H)═NO(arylalkyl)and —C(alkyl)=NO(arylalkyl);R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl), alkylN(H)C(═O)N(alkyl)₂,-alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)and -alkyl-C(═O)N(alkyl)₂;

R₈ is —C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b),

R_(8a) and R_(8b) are, at each occurrence, independently selected fromthe group consisting of alkyl, arylalkyl and heteroarylalkyl; whereineach R_(8a) and R_(8b) is independently substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of alkyl,nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl;R₉ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₉ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(9a);R_(9a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(9a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₀ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₀ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(10a);R_(10a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(10a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₁ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₁ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(11a);R_(11a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(11a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₂ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl orcycloalkenylalkyl; wherein each R₁₂ is substituted with 0, 1 or 2substituents independently selected from the group consisting ofhydroxy, alkoxy cyano, nitro and halo;R₁₃ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle; wherein each R₁₃ is substituted with 0, 1, 2or 3 substituents independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(13a);R_(13a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(13a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or 2.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, X is O and Y is O.

For example, the present invention provides a compound of formula (I)wherein wherein R₁ is OH, R₂ is H, X is O, Y is O, and R₃ is alkyl,cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl,arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a) or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is aryl or heteroaryl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is phenyl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a),and R is phenylmethyl wherein R_(4a) and R_(4b) are independentlyselected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), Ris phenylmethyl and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), Ris phenylmethyl and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (I)wherein R₁ is OH, R₂ is H, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), Ris phenylmethyl and R₇ is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5alkyl; wherein R_(4a) and R_(4b) are independently selected from thegroup consisting of hydrogen and alkyl.

Exemplary compounds of the present invention having formula (I) include,but not limited to, the following:

-   hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   tetrahydro-3-furanyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}acetamide;-   N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(2,6-dimethylphenoxy)acetamide;-   (3aS,7aR)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate    and    (3aR,7aS)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   3-furylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   2-pyridinylmethyl    2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-2-oxoethylcarbamate;-   2-(methylsulfonyl)ethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   (3aS,7aR)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   (3aR,7aS)-hexahydro-4H-furo[2,3-b]pyran-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   3-pyridinylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   4-pyridinylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;-   1,3-thiazol-5-ylmethyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate;    and-   N-{(2R,3S)-2-hydroxy-3-[({4-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-4-phenylbutyl}-4-[(E)-(hydroxyimino)methyl]-N-isobutylbenzenesulfonamide;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a second embodiment, the present invention provides a compound offormula (II)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(ROC(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxy, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b), -alkylN(ROC(═O)OR_(a),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))SO₂R_(a) or-alkylN(R_(b))SO₂NR_(a)R_(b); wherein each of the cycloalkyl,cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of thecycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl,hetrocycle moiety of the heterocyclealkyl, heteroaryl moiety of theheteroarylalkyl, aryl moiety of the arylalkyl is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl), alkylN(H)C(═O)N(alkyl)₂,-alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)and -alkyl-C(═O)N(alkyl)₂;

R₈ is —C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b),

R_(8a) and R_(8b) are, at each occurrence, independently selected fromthe group consisting of alkyl, arylalkyl and heteroarylalkyl; whereineach R_(8a) and R_(8b) is independently substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of alkyl,nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); andR_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H and R₃ is alkyl, cycloalkenylalkyl,cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl,hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a)or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkyl and R₄ is aryl orheteroaryl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl and R₄ isphenyl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl and R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) are independentlyselected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a),and R₇ is alkyl; wherein R_(4a) and R_(4b) are independently selectedfrom the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is alkyl or cycloalkylalkyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is alkyl and R is phenylmethyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is alkyl and R is phenylmethyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (II)wherein R₁ is OH, R₂ is H, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5 alkyl and R isphenylmethyl; wherein R_(4a) and R_(4b) are independently selected fromthe group consisting of hydrogen and alkyl.

Exemplary compounds of the present invention of formula (II) include,but not limited to, the following:

-   tert-butyl    (1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate;-   benzyl(1S)-3-amino-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-oxopropylcarbamate;-   methyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate;-   2-pyridinylmethyl(1R)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate;-   2-pyridinylmethyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate;-   benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropylcarbamate;-   benzyl(1S,2R)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-hydroxypropylcarbamate;-   tert-butyl(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutylcarbamate;-   benzyl(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutylcarbamate;-   tert-butyl    (1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-(methylsulfonyl)propylcarbamate;-   benzyl(1R)-1-[(aminosulfonyl)methyl]-2({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-2-oxoethylcarbamate;-   benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-(methylsulfanyl)propylcarbamate;-   benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-3-methylbutylcarbamate;-   benzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamate;-   benzyl(1S)-4-amino-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamate;-   benzyl(1S)-2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-1-(1H-imidazol-4-ylmethyl)-2-oxoethylcarbamate;-   benzyl(1S)-2-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate;-   benzyl(1S,2R)-2-(2-amino-2-oxoethoxy)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]propylcarbamate;-   methyl(3S)-4-({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)-3-{[(benzyloxy)carbonyl]amino}-4-oxobutanoate;-   2-pyridinylmethyl(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutylcarbamate;-   [6-(methoxymethyl)-2-pyridinyl]methyl(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutylcarbamate;-   [6-(methoxymethyl)-2-pyridinyl]methyl(1S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2,2-dimethylpropylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide;-   (2R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({[(5-nitro-3-thienyl)methyl]amino}acetyl)amino]pentanamide;    and-   benzyl(1S)-4-{[amino(imino)methyl]amino}-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamate;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a third embodiment, the present invention provides a compound offormula (III)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein

X is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —SR_(a), —SOR_(a),—SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R^(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(1a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂;R₉ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₉ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(9a);R_(9a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(9a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl),-alkyl-N(alkyl)₂, -alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or 2.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O and R₃ is alkyl, cycloalkenylalkyl,cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl,hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a)or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkyl and R₄ isaryl or heteroaryl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl and R₄is phenyl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl and R₄is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected fromthe group consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) are independentlyselected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), R₇ is alkyl and R is phenylmethyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b), and —C(R_(4b))═NOR_(4a),and R₇ is alkyl and R is phenylmethyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (III)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a),and R₇ is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl and R isphenylmethyl; wherein R_(4a) and R_(4b) are independently selected fromthe group consisting of hydrogen and alkyl.

Exemplary compounds of the present invention of formula (III) include,but not limited to, the following:

-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxoimidazolidin-1-yl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(tetrahydro-2-furanylmethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[2-(dimethylamino)ethyl]({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(2-furylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(2-pyridinylmethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2,5-dimethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-(3-nitrobenzyl)-2-oxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(2-methoxyethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(4-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(4-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(2-hydroxypropyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)[2-(2-thienyl)ethyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)-2-[3-(1H-benzimidazol-5-ylmethyl)-2-oxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)[(1S)-1-(hydroxymethyl)-2-methylpropyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)[(1R)-1-(hydroxymethyl)-2-methylpropyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(4-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(2-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(methoxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3-methyl-pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-(3-{[6-(methoxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-(3-cyanobenzyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-(2-oxo-3-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(8-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(8-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]-4-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(7-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(6-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-(2-oxo-3-{[2-(2-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(7-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(6-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[(E)-(dimethylhydrazono)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(neopentyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N4(1S,2R)-1-benzyl-2-hydroxy-3-{({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)[4-(2-pyridinyl)benzyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(1E)-N-hydroxyethanimidoyl]-4-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({6-[(1E)-N-hydroxyethanimidoyl]-2-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)-2-{3-[(6-{[acetyl(methyl)amino]methyl}-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-(3-{[2-(1-methylhydrazino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{2-oxo-3-[(6-pyridin-2-yl-2-pyridinyl)methyl]-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-4-quinolinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(4-methyl-2-quinolinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(6-isopropyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(4-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[4-(methoxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]butanamide;-   (2S,3S)-2-{3-[(2-{[acetyl(methyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-{3-[(2-methyl-4-quinolinyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-[2-oxo-3-(6-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-[2-oxo-3-(7-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(2-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   {4-[(3-{(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methyl    acetate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(methoxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{2-oxo-3-[3-(3-pyridinyl)benzyl]-1-imidazolidinyl}pentanamide;-   (2S)-2-[3-({2-[(1S)-1-(acetylamino)ethyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(3-{[2-(6-methyl-3-pyridinyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(4-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(2-thienyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(6-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   ethyl    {6-[(3-{(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutyl}-2-oxo-1-imidazolidinyl)methyl]-2-pyridinyl}methyl(methyl)carbamate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(hydroxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{2-oxo-3-[3-(1,3-thiazol-2-yl)benzyl]-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{2-oxo-3-[3-(2-pyridinyl)benzyl]-1-imidazolidinyl}pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(3-{[2-(5-methyl-3-isoxazolyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2,4-dimethyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[3-(3-furyl)benzyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{2-oxo-3-[3-(4-pyrimidinyl)benzyl]-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(6-methoxy-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(2-pyrazinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-{3-[(6-methyl-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-[2-oxo-3-(4-pyridazinylmethyl)-1-imidazolidinyl]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(4-pyridazinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(3-pyridazinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxoimidazolidin-1-yl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(pyrrolidin-2-ylmethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide;-   (2S)-2-[3-(3-aminobenzyl)-2-oxoimidazolidin-1-yl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-oxido-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-oxidopyridin-4-yl)methyl]-2-oxoimidazolidin-1-yl}pentanamide;-   (2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxoimidazolidin-1-yl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]pyridin-4-yl}methyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-3-methylpentanamide;-   (2R,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)-2-(3-{3-[amino(hydroxyimino)methyl]benzyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[3-(hydroxymethyl)benzyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({6-[(hydroxyimino)methyl]-2-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-2,3-dimethylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(1-hydroxyethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(3-thienylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(1,3-thiazol-2-ylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(5-ethyl-2-phenyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(5-ethyl-2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2,5-dimethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)-2-[3-(1-benzothien-3-ylmethyl)-2-oxo-1-imidazolidinyl]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(1-methyl-1H-indol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-cyclopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)-2-{3-[(2-acetyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-isobutyryl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-butyryl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(5-nitro-2-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-nitro-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)-2(3-{[2-(azidomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N4(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{2-oxo-3-[(2-propionyl-1,3-thiazol-4-yl)methyl]-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3,3-dimethyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanediamide;-   (4-{[34(1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2-oxo-1-imidazolidinyl]methyl}-1,3-thiazol-2-yl)methyl    acetate;-   (2S)—N′    4(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}pentanediamide;-   (2S)-2-[3-(1-benzofuran-2-ylmethyl)-2-oxo-1-imidazolidinyl]-N4(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(3-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(4-methoxy-5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylsulfanyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(cyanomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(8-hydroxy-2-quinolinyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(4-methoxy-2-quinolinyl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(2-quinoxalinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-N⁴-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanediamide;-   (2S)—N¹-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-N⁴-ethyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanediamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)-2-[3-(1H-benzimidazol-5-ylmethyl)-2-oxo-1-imidazolidinyl]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[2-oxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-(3-cyanobenzyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-(formylamino)-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}propanamide;-   (2S)-3-[(aminocarbonyl)amino]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}propanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[6-(methoxymethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(1E)-N-hydroxyethanimidoyl]-4-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-(2-oxo-3-{[2-(2-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3,3-dimethyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-(3-{[2-(2-methyl-1,3-thiazol-4-yl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(2-ethyl-4-pyridinyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-(3-{[2-(6-methyl-3-pyridinyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)pentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3,3-dimethyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-3-methyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](neopentyl)amino]propyl}-3-methyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanamide;-   (2S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)-2-[3-({2-[(acetylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-{[(methylsulfonyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(hydroxyimino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide;-   methyl(4-{[3-((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2-oxo-1-imidazolidinyl]methyl}-1,3-thiazol-2-yl)methylcarbamate;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylsulfonyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(diethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isopropylamino)-2-oxoethyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[N-hydroxyethanimidoyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-3-methylpentanamide;-   (2S,3S)-2-(3-{3-[amino(hydroxyimino)methyl]benzyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-4-hydroxy-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1R,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}phenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,5-dichloro-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-hydroxy-3-[(3-pyridinylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-hydroxy-3-[(methylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-cyclopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-cyclopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-cyclopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-ethyl-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,5-dichloro-2-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl({4-[(methylsulfonyl)amino]phenyl}sulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-fluoro-4-hydroxy-2-methylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-chloro-4-hydroxy-2-methylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-chloro-4-hydroxy-5-methylphenyl)sulfonyl]isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-{[(methylamino)sulfonyl]amino}phenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   ethyl    2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}phenylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-isopropylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3,5-dimethylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-nitro-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(4-amino-3-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   {4-[(3-{(1S)-1-[({(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}amino)carbonyl]-2-methylpropyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methyl    acetate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-hydroxy-3-(methylamino)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[3-(dimethylamino)-4-hydroxyphenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-{[(ethylamino)carbonyl]amino}-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   methyl    2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}phenylcarbamate;-   benzyl    2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}phenylcarbamate;-   (2S)—N-{(1S,2R)-3-[[(1-acetyl-2,3-dihydro-1H-indol-5-yl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(2-chloro-4-hydroxy-5-methylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-acetyl-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(2-amino-1,3-thiazol-5-yl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-(3-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-(2-hydroxyethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-cyano-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}pentanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(1H-benzimidazol-5-ylmethyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]pentanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3,3-dimethyl-2-(2-oxo-3-{[2-(3-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-(3-{[2-(2-methyl-1,3-thiazol-4-yl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(neopentyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(3-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-chlorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-fluorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,4-dibromophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-bromo-5-chloro-2-pyridinyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-fluorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-bromophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-chloro-4-fluorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,4-dimethoxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,4-dichlorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(4-acetylphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2,4,6-trichlorophenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(2-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(2,5-dichloro-3-thienyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl(2-thienylsulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(2,4-dichlorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(2,3-dichlorophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3,5-dimethyl-4-isoxazolyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-methoxy-4-methylphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[{[4-(acetylamino)-3-chlorophenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}benzoic    acid;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-fluoro-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl(5-isoquinolinylsulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(3,4,5-trimethoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(3-chloro-4-methylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[2-chloro-5-(trifluoromethyl)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   4-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}benzoic    acid;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl(phenylsulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-bromo-2-methoxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-vinylphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(2,3-dihydro-1-benzofuran-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-(1-hydroxyethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[(1-benzofuran-5-ylsulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl(3-pyridinylsulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[{[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-methyl-2,3-dihydro-1-benzofuran-5-yl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-{(Z)-[(benzyloxy)imino]methyl}-2-furyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   methyl    3-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}benzoate;-   (2S)—N-{(1S,2R)-3-[[(3-acetylphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(1-oxido-4-pyridinyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(3-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-bromo-2-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[4-(1,2-dihydroxyethyl)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(4-formylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-(hydroxymethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-Oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[4-(formylamino)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[{[3-(acetylamino)-4-hydroxyphenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   tert-butyl    2-(2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}anilino)-2-oxoethylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-3-[{[3-(formylamino)-4-hydroxyphenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-hydroxy-3-[(phenylacetyl)amino]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   tert-butyl    3-(2-hydroxy-5-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}anilino)-3-oxopropylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl({4-[(methoxyimino)methyl]phenyl}sulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(2,3-dihydro-1H-indol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[({3-[(3-aminopropanoyl)amino]-4-hydroxyphenyl}sulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   tert-butyl    2-(3-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}anilino)-2-oxoethylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[3-(hydroxymethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[[(5-formyl-2-furyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({5-[(E)-(hydroxyimino)methyl]-2-furyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({5-[(Z)-(hydroxyimino)methyl]-2-furyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[({4-[amino(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide;-   4-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}benzamide;-   4-{[[(2R,3S)-2-hydroxy-3-({(2S,3S)-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanoyl}amino)-4-phenylbutyl](isobutyl)amino]sulfonyl}benzamide;    and-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[[(4-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a fourth embodiment, the present invention provides a compound offormula (IV)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein

X is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl nitro,hydroxy, alkoxy, —NH₃—N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSOR_(a),-alkylSO₂R_(a), -alkylNR_(a)R_(b), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))SO₂R_(a) or-alkylN(R_(b))SO₂NR_(a)R_(b); wherein each of the cycloalkyl,cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkyl moiety of thecycloalkylalkyl, cycloalkenyl moiety of the cycloalkenylalkyl,hetrocycle moiety of the heterocyclealkyl, heteroaryl moiety of theheteroarylalkyl, aryl moiety of the arylalkyl is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂;R₁₀ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₀ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(10a);R_(10a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(10a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); and R_(c) is aryl, heteroaryl orheterocycle; wherein each II, is independently substituted with 0, 1, 2,3 or 4 substituents independently selected from the group consisting ofhalo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O and R₃ is alkyl, cycloalkenylalkyl,cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl,hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a)or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkyl and R₄ isaryl or heteroaryl.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkyl and R₄ isphenyl.

For example, the present invention provides a compound of formula (IV)wherein R₄ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl and R₄is phenyl substituted with 0, 1, 2, 3 or 4 substituents selected fromthe group consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) are independentlyselected from the group consisting of hydrogen or alkyl.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen or alkyl.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), R₇ is alkyl and R is phenylmethyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen or alkyl.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is alkyl and R is phenylmethyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen or alkyl.

For example, the present invention provides a compound of formula (IV)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5 alkyl and R isphenylmethyl; wherein R_(4a) and R_(4b) are independently selected fromthe group consisting of hydrogen or alkyl.

Exemplary compounds of the present invention of formula (IV) include,but not limited to, the following:

-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-imidazol-1-yl}butanamide;    and-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]pyridin-4-yl}methyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-3-methylpentanamide;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a fifth embodiment, the present invention provides a compound offormula (V)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein

X is O, S or NH; Y is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl), alkylN(H)C(═O)N(alkyl)₂,-alkylC(═O)OH, -alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)and -alkyl-C(═O)N(alkyl)₂;R₁₁ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₁ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b),—C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b),—C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(11a);R_(11a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(11a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) -alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or 2.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O and R₃ is alkyl,cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl,arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a) or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl or cycloalkyl andR₄ is aryl or heteroaryl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl or cycloalkyl andR₄ is phenyl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇ is alkyl and R isphenylmethyl; wherein R_(4a) and R_(4b) are independently selected fromthe group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is C3 alkyl, C4 alkyl, C5alkyl, cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), R₇ is alkyl and R is phenylmethyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.

For example, the present invention provides a compound of formula (V)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is C3 alkyl, C4 alkyl, C5alkyl, cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(11a)R_(11b) and—C(R_(4b))═NOR_(4a), R₇ is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5alkyl and R is phenylmethyl; wherein R_(4a) and R_(4b) are independentlyselected from the group consisting of hydrogen and alkyl.

Exemplary compounds of the present invention of formula (V) include, butnot limited to, the following:

-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-(3-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)-2-[3-(1,3-benzodioxol-5-ylmethyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   2-(3-benzyl-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}acetamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(4-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(2-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)-2-(3-benzyl-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)-2-[3-(3-acetylbenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2-cyano-4-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)-2-{3-[(2-acetyl-4-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)-2-{3-[3-(azidomethyl)benzyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(4-pyridinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(2-pyrazinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-(3-{3-[(methylamino)methyl]benzyl}-2,4-dioxo-1-imidazolidinyl)butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-(3-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S,3S)-2-{3-[(6-amino-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)-2-{3-[(2-acetyl-4-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(2-pyridinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S)-2-[3-(3-aminobenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{3-[N-hydroxyethanimidoyl]benzyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)-2-{3-[3-(aminomethyl)benzyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide;-   (2S,3S)-2-[3-(3-aminobenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]-4-pyridinyl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)-2-(3-benzyl-2,4-dioxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[2,4-dioxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   ethyl[3-((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2,5-dioxo-1-imidazolidinyl]acetate;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(6-methoxy-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(6-nitro-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)-2-{3-[(6-amino-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylpentanamide;-   (2S,3S)-2-{3-[(6-amino-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](neopentyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylpentanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isopropylamino)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isobutylamino)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[2-(4-morpholinyl)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(dimethylamino)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)-2-[3-(2-anilino-2-oxoethyl)-2,4-dioxo-1-imidazolidinyl]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-(3-{[2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-benzyl-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(3-methylbenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl]isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(2-cyanobenzyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(3-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{2,4-dioxo-3-[3-(trifluoromethoxy)benzyl]-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{2,4-dioxo-3-[4-(trifluoromethoxy)benzyl]-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(4-methylbenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(4-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(2-quinolinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-([1,1′-biphenyl]-4-ylmethyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(4-benzoylbenzyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(1-naphthylmethyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(2-naphthylmethyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(4-vinylbenzyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(4-methyl-3-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(2-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(2-methyl-3-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{2,4-dioxo-3-[4-(1,2,3-thiadiazol-4-yl)benzyl]-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(2-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(4-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(2-methoxy-5-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(2-fluoro-6-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-[3-(3-methyl-4-nitrobenzyl)-2,4-dioxo-1-imidazolidinyl]butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[3-(methoxymethyl)benzyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(3-bromobenzyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)-2-[3-(3-acetylbenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{2,4-dioxo-3-[3-(2-pyrazinyl)benzyl]-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{2,4-dioxo-3-[3-(2-thienyl)benzyl]-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(5-nitro-3-thienyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(6-chloro-1,3-benzodioxol-5-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[3-(1,3-benzothiazol-2-ylmethyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(6-nitro-1,3-benzodioxol-5-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)-2-[3-(1,3-benzodioxol-5-ylmethyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-2-[2,4-dioxo-3-(2-pyridinylmethyl)-1-imidazolidinyl]-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(4-methyl-3-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;-   (2S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-cyano-4-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S)-2-{3-[(2-acetyl-4-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-methylphenyl)sulfonyl](isobutyl)amino]propyl}-3-methylbutanamide;-   (2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[3-(hydroxymethyl)benzyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide;-   (2S,3S)-2-(3-{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-{3-[(6-amino-2-quinolinyl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-[2,4-dioxo-3-(4-quinolinylmethyl)-1-imidazolidinyl]-3-methylpentanamide;    and-   (2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(cyclopentylmethyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a sixth embodiment the present invention provides a compound offormula (VI)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein

X is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is H and R₂ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a); orR₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂;R₁₂ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl orcycloalkenylalkyl; wherein each R₁₂ is substituted with 0, 1 or 2substituents independently selected from the group consisting ofhydroxy, alkoxy cyano, nitro and halo;R₁₃ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle; wherein each R₁₃ is substituted with 0, 1, 2or 3 substituents independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(13a);R_(13a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(13a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); andR_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O and R₃ is alkyl, cycloalkenylalkyl,cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl, arylalkyl,hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a)or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkyl and R₄ isaryl or heteroaryl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl and R₄is phenyl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), R₇ is alkyl and R₁₂ is alkyl; wherein R_(4a) andR_(4b) are independently selected from the group consisting of hydrogenand alkyl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl, R₄ isphenyl substituted with 0, 1, 2, 3 or 4 substituents selected from thegroup consisting of halo, —OR_(4a), —NR_(4a)R_(4b) and—C(R_(4b))═NOR_(4a), R₇ is alkyl, R₁₂ is alkyl and R is phenylmethyl;wherein R_(4a) and R_(4b) are independently selected from the groupconsisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is alkyl, R₁₂ is methyl or ethyl, and R is phenylmethyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.

For example, the present invention provides a compound of formula (VI)wherein R₁ is OH, R₂ is H, X is O, R₃ is C3 alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R₇is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5 alkyl, R₁₂ is methyl orethyl, and R is phenylmethyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

Exemplary compounds of the present invention of formula (VI) include,but not limited to, the following:

-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[({ethyl[(2-isopropyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]propanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-tert-butoxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-tert-butoxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(3-nitrobenzyl)amino]carbonyl}amino)pentanamide;-   methyl    4-{(5S,8S,9R)-8-benzyl-9-hydroxy-11-({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)-2,13-dimethyl-5-[(1S)-1-methylpropyl]-3,6-dioxo-2,4,7,11-tetraazatetradec-1-yl}-1,3-thiazol-2-ylcarbamate;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylbutanamide;-   (2S,3S)-2-({[{[2-(acetylamino)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(3-pyridinylmethyl)amino]carbonyl}amino)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methyl-2-({[methyl(4-pyridinylmethyl)amino]carbonyl}amino)pentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(methoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanamide;-   (2S,3S)-2-({[({6-[(Z)-amino(hydroxyimino)methyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(methoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3,3-dimethylbutanamide;-   (2S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[{[6-(tert-butoxymethyl)-2-pyridinyl]methyl}(methyl)amino]carbonyl}amino)-3,3-dimethylbutanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide;-   (2S,3S)-2-({[(3-aminobenzyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide;-   (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide;-   (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-({[({2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)-2-({[({2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;-   (2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[({6-[N-hydroxyethanimidoyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-3-methylpentanamide;    and-   (2S,3S)-2-({[({2-[(1S)-1-(acetylamino)ethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide;    or a pharmaceutically acceptable salt form, stereoisomer, ester,    salt of an ester, prodrug, salt of a prodrug, or combination    thereof.

In a seventh embodiment, the present invention provides a compound offormula (VII)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein:

A is R₅C(O)—, R₆SO₂—,

X is O, S or NH; Y is O, S or NH;

R is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl;R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(E), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a);

R₂ is H;

R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a);R_(3a) is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle,wherein each R_(3a) is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of halo,nitro, cyano, formyl, alkyl, alkenyl, alkynyl, hydroxyl, alkoxy, —SH,—S(alkyl), —SO₂(alkyl), —NH₂, —N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(O)N(alkyl)₂, —C(═O)alkyl, haloalkyl, hydroxyalkyl,alkoxyalkyl, cyanoalkyl, formylalkyl, nitroalkyl, -alkylSH,-alkylS(alkyl), -alkylSO₂(alkyl), -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl, -alkylN(alkyl)C(═O)alkyl,-alkylC(═O)OH, -alkylC(═O)O(alkyl), -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and -alkylC(═O)alkyl;R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl whereineach R₄ is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of halo, alkyl, oxo, alkenyl,alkynyl, nitro, cyano, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a), —SO₂R_(4a), —NR_(4a)R_(4b),—OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a), —C(═O)NR_(4a)R_(4b),—N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a), —N(R_(4b))SO₂R_(4a),—N(R_(4b))C(═O)NR_(4a)R_(4b), —N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a),-alkylSOR_(4a), -alkylSO₂R_(4a), -alkylNR_(4a)R_(4b),-alkylOC(═O)R_(4a), -alkylC(═O)R_(4a), -alkylC(═O)OR_(4a),-alkylC(═O)NR_(4a)R_(4b), -alkylN(R_(4b))C(═O)R_(4a),-alkylN(R_(4b))C(═O)OR_(4a), -alkylN(R_(4b))SO₂R_(4a),-alkylN(R_(4b))C(═O)NR_(4a)R_(4b), -alkylN(R_(4b))SO₂NR_(4a)R_(4b),—N(H)C(═O)alkylN(H)C(═O)OR_(4a), —N(H)C(═O)alkylNR_(4a)R_(4b),—C(R_(4b))═NOR_(4a), —C(NR_(4a)R_(4b))═NOR_(4a) and—C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl;R₅ is alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -OalkylSO₂alkyl, —O-heterocycle, -alkyl-O-aryl or—O-alkyl-heteroaryl; wherein the heterocycle, aryl or heteroaryl moietyof —O-heterocycle, -alkyl-O-aryl and —O-alkyl-heteroaryl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂;R₆ is aryl or heteroaryl; wherein each R₆ is substituted with 0 or 1substituent selected from the group consisting of —C(H)═NOH,—C(alkyl)=NOH, —C(H)═NO(alkyl), —C(alkyl)=NO(alkyl), —C(H)═NO(arylalkyl)and —C(alkyl)=NO(arylalkyl);R₇ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, arylor heteroaryl; wherein each R₇ is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,—OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b),—C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂;

R₈ is —C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b),

R_(8a) and R_(8b) are, at each occurrence, independently selected fromthe group consisting of alkyl, arylalkyl and heteroarylalkyl; whereineach R_(8a) and R_(8b) is independently substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of alkyl,nitro, hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl;R₉ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₉ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(9a);R_(9a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(9a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₀ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₀ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b),—C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b),—C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(10a);R_(10a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(10a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₁ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a),cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₁ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b),—C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b),—C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(11a);R_(11a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(11a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R₁₂ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl orcycloalkenylalkyl; wherein each R₁₂ is substituted with 0, 1 or 2substituents independently selected from the group consisting ofhydroxy, alkoxy cyano, nitro and halo;R₁₃ is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle; wherein each R₁₃ is substituted with 0, 1, 2or 3 substituents independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(ROC(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(ROC(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b),—C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl,nitroalkyl, cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(ROC(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(13a);R_(13a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(13a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂;R_(a) and R_(b) at each occurrence are independently selected from thegroup consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or 2.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH and R₂ is H.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O and Y is O.

For example, the present invention provides a compound of formula (VII)wherein wherein R₁ is OH, R₂ is H, X is O, Y is O and R₃ is alkyl,cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl, heteroarylalkyl,arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR_(a), -alkylSOR_(a),-alkylSO₂R_(a) or -alkylNR_(a)R_(b).

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₁ is aryl or heteroaryl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₁ is phenyl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), and R is phenylmethyl; whereinR_(4a) and R_(4b) are independently selected from the group consistingof hydrogen and alkyl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), R is phenylmethyl and R₇ isalkyl; wherein R_(4a) and R_(4b) are independently selected from thegroup consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, R₃ is C3, alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), Ris phenylmethyl and R₇ is alkyl; wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.

For example, the present invention provides a compound of formula (VII)wherein R₁ is OH, R₂ is H, R₃ is C3, alkyl, C4 alkyl, C5 alkyl,cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, R₄ is phenylsubstituted with 0, 1, 2, 3 or 4 substituents selected from the groupconsisting of halo, —OR_(4a), —NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), Ris phenylmethyl and R₇ is C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl or C5alkyl; wherein R_(4a) and R_(4b) are independently selected from thegroup consisting of hydrogen and alkyl.

In an eighth embodiment, the present invention provides a pharmaceuticalcomposition comprising a therapeutically effective amount of a compound,or combination of compounds of formula (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, and a pharmaceutically acceptable carrier.

In a ninth embodiment, the present invention provides a pharmaceuticalcomposition comprising a therapeutically effective amount of a compoundor combination of compounds of formula (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two, three, five or six second HIV protease inhibitors,and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of ane ester, prodrug, salt of a prodrug, or combination thereof,one, two, three, four, five or six second HIV protease inhibitorsselected from the group consisting of ritonavir, lopinavir, saquinavir,amprenavir, fosamprenavir, nelfinavir, tipranavir, indinavir,atazanavir, TMC-126, TMC-114, mozenavir (DMP-450), JE-2147 (AG1776),L-756423, RO0334649, KNI-272, DPC-681, DPC-684 and GW640385X, and apharmaceutically acceptable carrier.

In a tenth embodiment the present invention provides a pharmaceuticalcomposition comprising a therapeutically effective amount of a compoundor combination of compounds of formula (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two, three, four, five or six HIV reverse transcriptaseinhibitors, and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound, orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of an ester, prodrug, salt of a prodrug, or combination thereof,one, two, three, four, five or six HIV reverse transcriptase inhibitorsselected from the group consisting of lamivudine, stavudine, zidovudine,abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir,elvucitabine, alovudine, MIV-210, Racivir (±-FTC), D-D4FC (Reverset,DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirine,emivirine, calamide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150,TMC-120 and TMC-125, and a pharmaceutically acceptable carrier.

In an eleventh embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two, three, four, five or six HIV entry/fusioninhibitors, and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of an ester, prodrug, salt of a prodrug, or combination thereof,one, two, three, four, five or six HIV entry/fusion inhibitors selectedfrom the group consisting of enfuvirtide (T-20), T-1249, PRO 2000, PRO542, PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C (SCH-C),Schering D (SCH-D), TNX-355 and UK-427857, and a pharmaceuticallyacceptable carrier.

In a twelfth embodiment the present invention provides a pharmaceuticalcomposition comprising a therapeutically effective amount of a compoundor combination of compounds of formula (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two, three, four, five or six HIV integrase inhibitors,and a pharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of an ester, prodrug, salt of a prodrug, or combination thereof,one, two, three or four HIV integrase inhibitors selected from the groupconsisting of S-1360, zintevir (AR-177), L-870812 and L-870810, and apharmaceutically acceptable carrier.

In a thirteenth embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two, three, four, five or six HIVbudding/maturation inhibitors, and a pharmaceutically acceptablecarrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of an ester, prodrug, salt of a prodrug, or combination thereof,PA-457, and a pharmaceutically acceptable carrier.

In a fourteenth embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two or three second HIV protease inhibitors,one, two or three HIV reverse transcriptase inhibitors, and apharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formula (I), (II), (III), (IV), (V), (VI) or(VII), or a pharmaceutically acceptable salt form, stereoisomer, ester,salt of an ester, prodrug, salt of a prodrug, or combination thereof,one, two or three second HIV protease inhibitors selected from the groupconsisting of ritonavir, lopinavir, saquinavir, amprenavir,fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126,TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649,KNI-272, DPC-681, DPC-684 and GW640385X, one, two or three HIV reversetranscriptase inhibitors selected from the group consisting oflamivudine, stavudine, zidovudine, abacavir, zalcitabine, didanosine,tenofovir, emtricitabine, amdoxovir, elvucitabine, alovudine, MIV-210,Racivir (±-FTC), D-D4FC (Reverset, DPC-817), SPD754, nevirapine,delavirdine, efavirenz, capravirine, emivirine, calanolide A, GW5634,BMS-56190 (DPC-083), DPC-961, MIV-150, TMC-120 and TMC-125, and apharmaceutically acceptable carrier.

In a fifteenth embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two or three second HIV protease inhibitors,one, two or three HIV entry/fusion inhibitors, and a pharmaceuticallyacceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formulae (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two or three second HIV protease inhibitors selected fromthe group consisting of ritonavir, lopinavir, saquinavir, amprenavir,fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126,TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649,KNI-272, DPC-681, DPC-684 and GW640385X, one, two or three HIVentry/fusion inhibitors selected from the group consisting ofenfuvirtide (T-20), T-1249, PRO 2000, PRO 542, PRO 140, AMD-3100,BMS-806, FP21399, GW873140, Schering C (SCH-C), Schering D (SCH-D),TNX-355 and UK-427857, and a pharmaceutically acceptable carrier.

In a sixteenth embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two or three second HIV protease inhibitors,one, two or three HIV integrase inhibitors, and a pharmaceuticallyacceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound, orcombination of compounds of formulae (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two or three second HIV protease inhibitors selected fromthe group consisting of ritonavir, lopinavir, saquinavir, amprenavir,fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126,TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649,KNI-272, DPC-681, DPC-684 and GW640385X, one, two or three HIV integraseinhibitors selected from the group consisting of S-1360, zintevir(AR-177), L-870812 and L-870810, and a pharmaceutically acceptablecarrier.

In a seventeenth embodiment the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof, one, two or three second HIV protease inhibitors,one, two or three HIV budding/maturation inhibitors, and apharmaceutically acceptable carrier.

For example, the present invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of a compound orcombination of compounds of formulae (I), (II), (III), (IV), (V), (VI)or (VII), or a pharmaceutically acceptable salt form, stereoisomer,ester, salt of an ester, prodrug, salt of a prodrug, or combinationthereof, one, two or three second HIV protease inhibitors selected fromthe group consisting of ritonavir, lopinavir, saquinavir, amprenavir,fosamprenavir, nelfinavir, tipranavir, indinavir, atazanavir, TMC-126,TMC-114, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, RO0334649,KNI-272, DPC-681, DPC-684 and GW640385X, PA-457, and a pharmaceuticallyacceptable carrier.

In an eighteenth embodiment, the present invention provides a method ofinhibiting the replication of an HIV virus comprising contacting saidvirus with a therapeutically effective amount of a compound orcombination of formula (I), (II), (III), (IV), (V), (VI) or (VII), or apharmaceutically acceptable salt form, stereoisomer, ester, salt of anester, prodrug, salt of a prodrug, or combination thereof.

In a nineteenth embodiment, the present invention provides a method ofinhibiting the replication of HIV comprising contacting said virus withany one of the pharmaceutical composition as disclosed hereinabove.

In a twentieth embodiment, the present invention provides a method oftreating or preventing an HIV infection comprising administering to apatient in need of such treatment a therapeutically effective amount ofa compound or combination of compounds of formula (I), (II), (III),(IV), (V), (VI) or (VII), or a pharmaceutically acceptable salt form,stereoisomer, ester, salt of an ester, prodrug, salt of a prodrug, orcombination thereof.

In a twenty-first embodiment the present invention provides a method oftreating or preventing an HIV infection comprising administering to apatient in need of such treatment any one of the pharmaceuticalcomposition as disclosed hereinabove.

In a twenty-second embodiment the present invention provides a method ofinhibiting an HIV protease comprising contacting said HIV protease witha therapeutically effective amount of a compound or combination offormula (I), (II), (III), (IV), (V), (VI) or (VII), or apharmaceutically acceptable salt form, stereoisomer, ester, salt of anester, prodrug, salt of a prodrug, or combination thereof.

In a twenty-third embodiment the present invention provides a method ofinhibiting an HIV protease comprising contacting said protease with anyone of the pharmaceutical compositions as disclosed hereinabove.

The term “N-protecting group” or “N-protected” as used herein refers tothose groups intended to protect the N-terminus of an amino acid orpeptide or to protect an amino group against undesirable reactionsduring synthetic procedures. Commonly used N-protecting groups aredisclosed in T. H. Greene and P. G. M. Wuts, Protective Groups inOrganic Synthesis, 2nd edition, John Wiley & Sons, New York (1991).N-protecting groups comprise acyl groups such as formyl, acetyl,propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl,trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl,benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like;sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl and the like;sulfenyl groups such as phenylsulfenyl (phenyl-S—),triphenylmethylsulfenyl (trityl-S—) and the like; sulfinyl groups suchas p-methylphenylsulfinyl (p-methylphenyl-S(O)—), t-butylsulfinyl(t-Bu-S(O)—) and the like; carbamate forming groups such asbenzyloxycarbonyl, p-chlorobenzyloxycarbonyl,p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl,2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl,3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl,2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl,2-nitro-4,5-dimethoxybenzyloxycarbonyl,3,4,5-trimethoxybenzyloxycarbonyl,1-(p-biphenylyl)-1-methylethoxycarbonyl,dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl,t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl,ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl,2,2,2-trichloro-ethoxy-carbonyl, phenoxycarbonyl,4-nitro-phenoxycarbonyl, fluorenyl-9-methoxycarbonyl,cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl,phenylthiocarbonyl and the like; alkyl groups such as benzyl,p-methoxybenzyl, triphenylmethyl, benzyloxymethyl and the like;p-methoxyphenyl and the like; and silyl groups such as trimethylsilyland the like. Preferred N-protecting groups include formyl, acetyl,benzoyl, pivaloyl, t-butylacetyl, phenylsulfonyl, benzyl,t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).

As used herein, the terms “S” and “R” configuration are as defined bythe IUPAC 1974 Recommendations for Section E, FundamentalStereochemistry, Pure Appl. Chem. (1976) 45, 13-30.

The compounds of the invention can comprise asymmetrically substitutedcarbon atoms. As a result, all stereoisomers of the compounds of theinvention are meant to be included in the invention, including racemicmixtures, mixtures of diastereomers, as well as individual opticalisomers, including, enantiomers and single diastereomers of thecompounds of the invention substantially free from their enantiomers orother diastereomers. By “substantially free” is meant greater than about80% free of other enantiomers or diastereomers of the compound, morepreferably greater than about 90% free of other enantiomers ordiastereomers of the compound, even more preferably greater than about95% free of other enantiomers or diastereomers of the compound, evenmore highly preferably greater than about 98% free of other enantiomersor diastereomers of the compound and most preferably greater than about99% free of other enantiomers or diastereomers of the compound.

In addition, compounds comprising the possible geometric isomers ofcarbon-carbon double bonds and carbon-nitrogen double are also meant tobe included in this invention.

Individual stereoisomers of the compounds of this invention can beprepared by any one of a number of methods which are within theknowledge of one of ordinary skill in the art. These methods includestereospecific synthesis, chromatographic separation of diastereomers,chromatographic resolution of enantiomers, conversion of enantiomers inan enantiomeric mixture to diastereomers and then chromatographicallyseparating the diastereomers and regeneration of the individualenantiomers, enzymatic resolution and the like.

Stereospecific synthesis involves the use of appropriate chiral startingmaterials and synthetic reactions which do not cause racemization orinversion of stereochemistry at the chiral centers.

Diastereomeric mixtures of compounds resulting from a synthetic reactioncan often be separated by chromatographic techniques which arewell-known to those of ordinary skill in the art.

Chromatographic resolution of enantiomers can be accomplished on chiralchromatography resins. Chromatography columns containing chiral resinsare commercially available. In practice, the racemate is placed insolution and loaded onto the column containing the chiral stationaryphase. The enantiomers are then separated by HPLC.

Resolution of enantiomers can also be accomplished by converting theenantiomers in the mixture to diastereomers by reaction with chiralauxiliaries. The resulting diastereomers can then be separated by columnchromatography. This technique is especially useful when the compoundsto be separated contain a carboxyl, amino or hydroxyl group that willform a salt or covalent bond with the chiral auxiliary. Chirally pureamino acids, organic carboxylic acids or organosulfonic acids areespecially useful as chiral auxiliaries. Once the diastereomers havebeen separated by chromatography, the individual enantiomers can beregenerated. Frequently, the chiral auxiliary can be recovered and usedagain.

Enzymes, such as esterases, phosphatases and lipases, can be useful forresolution of derivatives of the enantiomers in an enantiomeric mixture.For example, an ester derivative of a carboxyl group in the compounds tobe separated can be prepared. Certain enzymes will selectively hydrolyzeonly one of the enantiomers in the mixture. Then the resultingenantiomerically pure acid can be separated from the unhydrolyzed ester.

In addition, solvates and hydrates of the compounds of Formula (1),(II), (III), (IV), (V), (VI) or (VII), are meant to be included in thisinvention.

When any variable (for example A, R, R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉,R₁₀, R₁₁, R₁₂, R₁₃, R₁₄, R_(a), R_(b), R_(c), n, etc.) occurs more thanone time in any substituent or in the compound of formula (I), (II),(III), (IV), (V), (VI) or (VII), or any other formula herein, itsdefinition on each occurrence is independent of its definition at everyother occurrence. In addition, combinations of substituents arepermissible only if such combinations result in stable compounds. Stablecompounds are compounds which can be isolated in a useful degree ofpurity from a reaction mixture.

The compounds of the present invention can be used in the form of saltsderived from inorganic or organic acids. These salts include but are notlimited to the following: 4-acetamido-benzoate, acetate, adipate,alginate, carbonate, 4-chlorobenzenesulfonate, citrate, aspartate,benzoate, benzenesulfonate, bisulfate, butyrate, camphorate,camphorsulfonate, cholate, digluconate, cyclopentanepropionate,dichloroacetate, dodecylsulfate, ethanedisulfonate, ethanesulfonate,ethylsuccinate, formate, fumarate, galactarate, D-gluconate,D-glucuronate, glucoheptanoate, glutarate, lycerophosphate, glycolate,hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide,hydroiodide, 2-hydroxyethanesulfonate (isethionate),3-hydroxy-2-naphthoate, 1-hydroxy-2-naphthoate, lactate, lactobionate,laurate, maleate, malonate, mandelate, methanesulfonate, nicotinate,1,5-naphthalene-disulfonate, 2-naphthalenesulfonate, oleate, oxalate,pamoate, palmitate, pectinate, persulfate, 3-phenylpropionate, picrate,pivalate, propionate, L-pyroglutamate, sebacate, stearate, succinate,tartrate, terephthalate, thiocyanate, p-toluenesulfonate, undecanoate,undecylenoate and valerate. Also, the basic nitrogen-containing groupscan be quaternized with such agents as loweralkyl halides, such asmethyl, ethyl, propyl, and butyl chloride, bromides, and iodides;dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates,long chain halides such as decyl, lauryl, myristyl and stearylchlorides, bromides and iodides, aralkyl halides like benzyl andphenethyl bromides, and others. Water or oil-soluble or dispersibleproducts are thereby obtained.

Examples of acids which may be employed to form pharmaceuticallyacceptable acid addition salts include such inorganic acids ashydrochloric acid, sulphuric acid and phosphoric acid and such organicacids as oxalic acid, maleic acid, succinic acid and citric acid. Othersalts include salts with alkali metals or alkaline earth metals, such asaluminum, sodium, lithium, potassium, calcium, magnesium or zinc or withorganic bases such as diethylethanolamine, diethanolamine,ethylenediamine, guanidine, meglumine, olamine (ethnolamine),piperazine, piperidine, triethylamine, tromethamine, benzathine,benzene-ethanamine, adenine, cytosine, diethylamine, glucosamine,guanine, nicotinamide, hydrabamine, tributylamine, deanol, epolamine ortriethanolamine.

Representative salts of the compounds of the present invention include,but not limited to, hydrochloride, methanesulfonate, sulfonate,phosphonate, isethionate and trifluoroacetate.

The compounds of the present invention can also be used in the form ofprodrugs. Examples of such prodrugs include compounds wherein one, twoor three hydroxy groups in the compound of this invention arefunctionalized with R¹⁵ wherein R¹⁵ is

wherein

R₁₀₃ is C(R₁₀₅)₂, O or —N(R₁₀₅);

R₁₀₄ is hydrogen, alkyl, haloalkyl, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl or dialkylaminocarbonyl,each M is independently selected from the group consisting of H, Li, Na,K, Mg, Ca, Ba, —N(R₁₀₅)₂, alkyl, alkenyl, and R₁₀₆; wherein 1 to 4 —CH₂radicals of the alkyl or alkenyl, other than the —CH₂ radical that isbound to Z, is optionally replaced by a heteroatom group selected fromthe group consisting of O, S, S(O), SO₂ and N(R₁₀₅); and wherein anyhydrogen in said alkyl, alkenyl or R₁₀₆ is optionally replaced with asubstituent selected from the group consisting of oxo, —OR₁₀₅, —R₁₀₅,—N(R₁₀₅)₂, —CN, —C(O)OR₁₀₅, —C(O)N(R₁₀₅)₂, —SO₂N(R₁₀₅),—N(R₁₀₅)C(O)R₁₀₅, —C(O)R₁₀₅, —S(O)R₁₀₅, —SO₂R₁₀₅, —OCF₃, —SR₁₀₆,—SOR₁₀₆, —SO₂R₁₀₆, —N(R₁₀₅)SO₂R₁₀₅, halo, —CF₃ and NO₂;Z is CH₂, O, S, —N(R₁₀₅), or, when M is absent, H;

Q is O or S;

W is P or S; wherein when W is S, Z is not S;M′ is H, alkyl, alkenyl or R₁₀₆; wherein 1 to 4 —CH₂ radicals of thealkyl or alkenyl is optionally replaced by a heteroatom group selectedfrom O, S, S(O), SO₂, or N(R₁₀₅); and wherein any hydrogen in saidalkyl, alkenyl or R₁₀₆ is optionally replaced with a substituentselected from the group consisting of oxo, —OR₁₀₅, —R₁₀₅, —N(R₁₀₅)₂,—CN, —C(O)OR₁₀₅, —C(O)N(R₁₀₅)₂, —SO₂N(R₁₀₅), —N(R₁₀₅)C(O)R₁₀₅,—C(O)R₁₀₅, —SR₁₀₅, —S(O)R₁₀₅, —SO₂R₁₀₅, —OCF₃, —SR₁₀₆, —SOR₁₀₆,—SO₂R₁₀₆, —N(R₁₀₅)SO₂R₁₀₅, halo, —CF₃ and NO₂;R₁₀₆ is a monocyclic or bicyclic ring system selected from the groupconsisting of aryl, cycloalkyl, cycloalkenyl heteroaryl and heterocycle;wherein any of said heteroaryl and heterocycle ring systems contains oneor more heteroatom selected from the group consisting of O, N, S, SO,SO₂ and N(R₁₀₅); and wherein any of said ring system is substituted with0, 1, 2, 3, 4, 5 or 6 substituents selected from the group consisting ofhydroxy, alkyl, alkoxy, and —OC(O)alkyl;each R₁₀₅ is independently selected from the group consisting of H oralkyl; wherein said alkyl is optionally substituted with a ring systemselected from the group consisting of aryl, cycloalkyl, cycloalkenyl,heteroaryl and heterocycle; wherein any of said heteroaryl andheterocycle ring systems contains one or more heteroatoms selected fromthe group consisting of O, N, S, SO, SO₂, and N(R₁₀₅); and wherein anyone of said ring system is substituted with 0, 1, 2, 3 or 4 substituentsselected from the group consisting of oxo, —OR₁₀₅, —R₁₀₅, —N(R₁₀₅)₂,—N(R₁₀₅)C(O)R₁₀₅, —C(O)OR₁₀₅, —C(O)N(R₁₀₅)₂, halo and —CF₃;q is 0 or 1;m is 0 or 1; andt is 0 or 1.

Representative examples of R¹⁵ of formula (VIII) or (IX) that can beutilized for the functionalization of the hydroxy groups in the compoundof the present invention include, but not limited to, the following:

It will be understood by those of skill in the art that component M orM′ in the formulae set forth herein will have either a covalent, acovalent/zwitterionic, or an ionic association with either Z or R₁₀₃depending upon the actual choice for M or M′. When M or M′ is hydrogen,alkyl, alkenyl or R₁₀₆, then M or M′, is covalently bound to —R₁₀₃ or Z.If M is a mono or bivalent metal or other charged species (i.e. NH₄ ⁺),there is an ionic interaction between M and Z and the resulting compoundis a salt.

These prodrugs of the compound of the present invention serve toincrease the solubility of these compounds in the gastrointestinaltract. These prodrugs also serve to increase solubility for intravenousadministration of the compound. These prodrugs may be prepared by usingconventional synthetic techniques. One of skill in the art would be wellaware of conventional synthetic reagents to convert one or more of thehydroxy groups of the compounds of the present invention to a desiredprodrug, functionalized by the substituents of formula (VIII) or (IX) asdefined above.

The prodrugs of this invention are metabolized in vivo to provide thecompound of this invention.

The compounds of the invention are useful for inhibiting retroviralprotease, in particular HIV protease, in vitro or in vivo (especially inmammals and in particular in humans). The compounds of the presentinvention are also useful for the inhibition of retroviruses in vivo,especially human immunodeficiency virus (HIV). The compounds of thepresent invention are also useful for the treatment or prophylaxis ofdiseases caused by retroviruses, especially acquired immune deficiencysyndrome or an HIV infection in a human or other mammal.

Total daily dose administered to a human or other mammal host in singleor divided doses may be in amounts, for example, from 0.001 to 300 mg/kgbody weight daily and more usually 0.1 to 20 mg/kg body weight daily.Dosage unit compositions may contain such amounts of submultiplesthereof to make up the daily dose.

The amount of active ingredient that may be combined with the carriermaterials to produce a single dosage form will vary depending upon thehost treated and the particular mode of administration.

It will be understood, however, that the specific dose level for anyparticular patient will depend upon a variety of factors including theactivity of the specific compound employed, the age, body weight,general health, sex, diet, time of administration, route ofadministration, rate of excretion, drug combination, and the severity ofthe particular disease undergoing therapy.

The compounds of the present invention may be administered orally,parenterally, sublingually, by inhalation spray, rectally, or topicallyin dosage unit formulations containing conventional nontoxicpharmaceutically acceptable carriers, adjuvants, and vehicles asdesired. Topical administration may also involve the use of transdermaladministration such as transdermal patches or iontophoresis devices. Theterm parenteral as used herein includes subcutaneous injections,intravenous, intramuscular, intrasternal injection, or infusiontechniques.

Injectable preparations, for example, sterile injectable aqueous oroleagenous suspensions may be formulated according to the known artusing suitable dispersing or wetting agents and suspending agents. Thesterile injectable preparation may also be a sterile injectable solutionor suspension in a nontoxic parenterally acceptable diluent or solvent,for example, as a solution in 1,3-propanediol. Among the acceptablevehicles and solvents that may be employed are water, Ringer's solution,and isotonic sodium chloride solution. In addition, sterile, fixed oilsare conventionally employed as a solvent or suspending medium. For thispurpose any bland fixed oil may be employed including synthetic mono- ordiglycerides. In addition, fatty acids such as oleic acid find use inthe preparation of injectables.

Suppositories for rectal administration of the drug can be prepared bymixing the drug with a suitable nonirritating excipient such as cocoabutter and polyethylene glycols which are solid at ordinary temperaturesbut liquid at the rectal temperature and will therefore melt in therectum and release the drug.

Solid dosage forms for oral administration may include capsules,tablets, pills, powders, and granules. In such solid dosage forms, theactive compound may be admixed with at least one inert diluent such assucrose lactose or starch. Such dosage forms may also comprise, as isnormal practice, additional substances other than inert diluents, e.g.,lubricating agents such as magnesium stearate. In the case of capsules,tablets, and pills, the dosage forms may also comprise buffering agents.Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration may include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, and elixirscontaining inert diluents commonly used in the art, such as water. Suchcompositions may also comprise adjuvants, such as wetting agents,emulsifying and suspending agents, and sweetening, flavoring, andperfuming agents.

The compounds of the present invention can also be administered in theform of liposomes. As is known in the art, liposomes are generallyderived from phospholipids or other lipid substances. Liposomes areformed by mono- or multi-lamellar hydrated liquid crystals that aredispersed in an aqueous medium. Any non-toxic, physiologicallyacceptable and metabolizable lipid capable of forming liposomes can beused. The present compositions in liposome form can contain, in additionto the compound of the present invention, stabilizers, preservatives,excipients, and the like. The preferred lipids are the phospholipids andphosphatidyl cholines (lecithins), both natureal and synthetic.

Methods to form liposomes are known in the art. See, for example,Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, NewYork, N.Y. (1976), p. 33.

While the compound of the invention can be administered as the soleactive pharmaceutical agent, it can also be used in combination with oneor more immunomodulators, antiviral agents, other antiinfective agentsor vaccines. Other antiviral agents to be administered in combinationwith a compound of the present invention include AL-721, betainterferon, polymannoacetate, reverse transcriptase inhibitors (forexample, BCH-189, AzdU, carbovir, ddA, d4C, d4T (stavudine), 3TC(lamivudine) DP-AZT, FLT (fluorothymidine), BCH-189,5-halo-3′-thia-dideoxycytidine, PMEA, bis-POMPMEA, zidovudine (AZT),MSA-300, trovirdine, R82193, L-697,661, BI-RG-587 (nevirapine),abacavir, zalcitabine, didanosine, tenofovir, emtricitabine, amdoxovir,elvucitabine, alovudine, MIV-210, Racivir (±-FTC), D-D4FC (Reverset,DPC-817), SPD754, nevirapine, delavirdine, efavirenz, capravirine,emivirine, calanolide A, GW5634, BMS-56190 (DPC-083), DPC-961, MIV-150,TMC-120, and TMC-125 and the like), retroviral protease inhibitors (forexample, HIV protease inhibitors such as ritonavir, lopinavir,saquinavir, amprenavir (VX-478), fosamprenavir, nelfinavir (AG1343),tipranavir, indinavir, atazanavir, TMC-126, TMC-114, mozenavir(DMP-450), JE-2147 (AG1776), L-756423, RO0334649, KNI-272, DPC-681,DPC-684, GW640385X, SC-52151, BMS 186,318, SC-55389a, BILA 1096 BS,DMP-323, KNI-227, and the like), HEPT compounds, L,697,639, R82150,U-87201E and the like), HIV integrase inhibitors (S-1360, zintevir(AR-177), L-870812 L-870810 and the like), TAT inhibitors (for example,RO-24-7429 and the like), trisodium phosphonoformate, HPA-23,eflonithine, Peptide T, Reticulose (nucleophosphoprotein), ansamycin LM427, trimetrexate, UA001, ribavirin, alpha interferon, oxetanocin,oxetanocin-G, cylobut-G, cyclobut-A, ara-M, BW882C87, foscarnet,BW256U87, BW348U87, L-693,989, BV ara-U, CMV triclonal antibodies, FIAC,HOE-602, HPMPC, MSL-109, TI-23, trifluridine, vidarabine, famciclovir,penciclovir, acyclovir, ganciclor, castanosperminem rCD4/CD4-IgG,CD4-PE40, butyl-DNJ, hypericin, oxamyristic acid, dextran sulfate andpentosan polysulfate. Other agents that can be administered incombination with the compound of the present invention include HIVentry/fusion inhibitor (enfuvirtide (T-20), T-1249, PRO 2000, PRO 542,PRO 140, AMD-3100, BMS-806, FP21399, GW873140, Schering C (SCH-C),Schering D (SCH-D), TNX-355, UK-427857 and the like) and HIVbudding/maturation inhibitor such as PA-457. Immunomodulators that canbe administered in combination with the compound of the presentinvention include bropirimine, Ampligen, anti-human alpha interferonantibody, colony stimulting factor, CL246,738, Imreg-1, Imreg-2,diethydithiocarbamate, interleukin-2, alpha-interferon, inosinepranobex, methionine enkephalin, muramyl-tripeptide, TP-5,erythropoietin, naltrexone, tumor necrosis factor, beta interferon,gamma interferon, interleukin-3, interleukin-4, autologous CD8+infusion, alpha interferon immunoglobulin, IGF-1, anti-Leu-3A,autovaccination, biostimulation, extracorporeal photophoresis,cyclosporin, rapamycin, FK-565, FK-506, G-CSF, GM-CSF, hyperthermia,isopinosine, IVIG, HIVIG, passive immunotherapy and polio vaccinehyperimmunization. Other antiinfective agents that can be administeredin combination with the compound of the present invention includepentamidine isethionate. Any of a variety of HIV or AIDS vaccines (forexample, gp120 (recombinant), Env 2-3 (gp120), HIVAC-1e (gp120), gp160(recombinant), VaxSyn HIV-1 (gp160), Immuno-Ag (gp160), HGP-30,HIV-Immunogen, p24 (recombinant), VaxSyn HIV-1 (p24)) can be used incombination with the compound of the present invention.

Other agents that can be used in combination with the compound of thisinventim are ansamycin LM 427, apurinic acid, ABPP, Al-721, carrisyn,AS-101, avarol, azimexon, colchicine, compound Q, CS-85, N-acetylcysteine, (2-oxothiazolidine-4-carboxylate), D-penicillamine,diphenylhydantoin, EL-10, erythropoieten, fusidic acid, glucan, HPA-23,human growth hormone, hydroxchloroquine, iscador, L-ofloxacin or otherquinolone antibiotics, lentinan, lithium carbonate, MM-1, monolaurin,MTP-PE, naltrexone, neurotropin, ozone, PAI, panax ginseng,pentofylline, pentoxifylline, Peptide T, pine cone extract,polymannoacetate, reticulose, retrogen, ribavirin, ribozymes, RS-47,Sdc-28, silicotungstate, THA, thymic humoral factor, thymopentin,thymosin fraction 5, thymosin alpha one, thymostimulin, UA001, uridine,vitamin B12 and wobemugos.

Other agents that can be used in combination with the compound of thisinvention are antifungals such as amphotericin B, clotrimazole,flucytosine, fluconazole, itraconazole, ketoconazole and nystatin andthe like.

Other agents that can be used in combination with the compound of thisinvention are antibacterials such as amikacin sulfate, azithromycin,ciprofloxacin, tosufloxacin, clarithromycin, clofazimine, ethambutol,isoniazid, pyrazinamide, rifabutin, rifampin, streptomycin and TLC G-65and the like.

Other agents that can be used in combination with the compound of thisinvention are anti-neoplastics such as alpha interferon, COMP(cyclophosphamide, vincristine, methotrexate and prednisone), etoposide,mBACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide,vincristine and dexamethasone), PRO-MACE/MOPP (prednisone, methotrexate(w/leucovin rescue), doxorubicin, cyclophosphamide, taxol,etoposide/mechlorethamine, vincristine, prednisone and procarbazine),vincristine, vinblastine, angioinhibins, pentosan polysulfate, plateletfactor 4 and SP-PG and the like.

Other agents that can be used in combination with the compound of thisinvention are drugs for treating neurological disease such as peptide T,ritalin, lithium, elavil, phenyloin, carbamazipine, mexitetine, heparinand cytosine arabinoside and the like.

Other agents that can be used in combination with the compound of thisinvention are anti-protozoals such as albendazole, azithromycin,clarithromycin, clindamycin, corticosteroids, dapsone, DIMP,eflornithine, 566C80, fansidar, furazolidone, L,671,329, letrazuril,metronidazole, paromycin, pefloxacin, pentamidine, piritrexim,primaquine, pyrimethamine, somatostatin, spiramycin, sulfadiazine,trimethoprim, TMP/SMX, trimetrexate and WR 6026 and the like.

For example, a compound of this invention can be administered incombination with ritonavir. Such a combination is especially useful forinhibiting HIV protease in a human.

Such a combination is also especially useful for inhibiting or treatingan HIV infection in a human. When used in such a combination thecompound of this invention and ritonavir can be administered as separateagents at the same or different times or they can be formulated as asingle composition comprising both compounds.

When administered in combination with a compound, or combination ofcompounds of this invention, ritonavir causes an improvement in thepharmacokinetics (i.e., increases half-life, increases the time to peakplasma concentration, increases blood levels) of the compound of thisinvention.

Another combination can comprise of a compound, or combination ofcompounds of the present invention with ritonavir and one or morereverse transcriptase inhibitors (for example, lamivudine, stavudine,zidovudine, abacavir, zalcitabine, didanosine, tenofovir, emtricitabine,amdoxovir, elvucitabine, alovudine, MIV-210, Racivir (±-FTC), D-D4FC(Reverset, DPC-817), SPD754, nevirapine, delavirdine, efavirenz,capravirine, emivirine, calanolide A, GW5634, BMS-56190 (DPC-083),DPC-961, MIV-150 TMC-120, TMC-125 and the like). Such a combination isuseful for inhibiting or treating an HIV infection in a human.

When used in such a combination the compound or combination of compoundsof the present invention and ritonavir and one or more reversetranscriptase inhibitors can be administered as separate agents at thesame or different times or they can be formulated as compositionscomprising two or more of the compounds.

It will be understood that agents which can be combined with thecompound of the present invention for the inhibition, treatment orprophylaxis of AIDS or an HIV infection are not limited to those listedabove, but include in principle any agents useful for the treatment orprophylaxis of AIDS or an HIV infection.

When administered as a combination, the therapeutic agents can beformulated as separate compositions which are given at the same time ordifferent times, or the therapeutic agents can be given as a singlecomposition.

The foregoing is merely illustrative of the invention and is notintended to limit the invention to the disclosed compounds. Variationsand changes which are obvious to one skilled in the art are intended tobe within the scope and nature of the invention which are defined in theappended claims.

Antiviral Activity Determination of Activity Against Wild-Type HIV orthe Passaged Variants

MT4 cells were infected with 0.003 multiplicity of infection (MOI) ofwild-type HIV-1 or the passaged mutant variants at 1×10⁶ cells/mL for 1h, washed twice to remove unabsorbed virus and resuspended to 1×10⁵cells/mL of medium, seeded in a 96-well plate at 1004/well, and treatedwith an equal volume of solution of inhibitor in a series of half logdilutions in RPMI 1640 (Rosewell Park Memorial Institute) media (Gibco)containing 10% fetal bovine serum (FBS), in triplicate. The finalconcentration of DMSO in all wells was 0.5%. The virus control culturewas treated in an identical manner except no inhibitor was added to themedium. The cell control was incubated in the absence of inhibitor orvirus. Plates were incubated for 5 days in a CO₂ incubator at 37° C. Onday 5, stock solution of3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (4mg/mL in PBS, Sigma cat. # M 5655) was added to each well at 25 μL perwell. Plates were further incubated for 4 hrs, then treated with 20%sodium dodecyl sulfate (SDS) plus 0.02 N HCl at 50 μL per well to lysethe cells. After an overnight incubation, optical density (O.D.) wasmeasured by reading the plates at 570/650 nm wavelengths on a Bio-Tekmicrotitre plate reader. Percent cytopathic effect (CPE) reduction wascalculated from the formula below:

((O.D. test well−O.D. infected control well)/(O.D. uninfected controlwell−O.D. infected control well))×100

EC₅₀ values were determined from the plot of log (Fa/Fu) vs.log(compound concentration) using the median-effect equation (Chou,1975, Proc. Int. Cong. Pharmacol. 6^(th) p. 619) wherein Fa is thefraction inhibited by the compound, and Fu is the fraction uninhibited(1-Fa).

When tested by the above method, the compounds of the present inventionexhibit EC₅₀ in the range of 1 nM to 100 nM.

Determination of Anti-HIV Activity in the Presence of Human Serum

The above antiviral assay was performed in 96-well tissue culture platescontaining 50% human serum (HS) (Sigma) plus 10% FBS (Gibco/BRL, GrandIsland, N.Y.). Compounds were dissolved in DMSO, diluted at half logconcentrations in DMSO, then transferred to media without serum at fourtimes the final concentration. These solutions were added to 96-wellplates at 50 μL per well, in triplicate. Cells were separately infectedwith 0.003 MOI of HIV-1 at 1×10⁶ cells/mL for 1 h, washed twice toremove unadsorbed virus and resuspended to 2×10⁵ cells/mL of mediawithout serum. The cell suspension (50 μL) was seeded at 1×10⁴ cells perwell. Uninfected cells were included as control. Final DMSOconcentration in all wells was 0.5% including uninfected and infectedcontrol wells. Cultures were incubated for 5 days in a CO₂ incubator at37° C. EC₅₀ values were measured using MTT uptake as described above.

When tested by the above method, compounds of the present inventionexhibit EC₅₀ in the range of 10 nM to 1 μM.

Generation of HIV-1 Resistant to ABT-378/r (A 17) by In Vitro Passage

MT4 cells (2×10⁶) were infected with pNL4-3 at an MOI of 0.03 for 2 h,washed, then cultured in the presence of ABT-378 and ritonavir atconcentration ratio of 5:1. The concentration of ABT-378 and ritonavirused in the initial passage was 1 nM and 0.2 nM respectively. Viralreplication was monitored by determination of p24 antigen levels in theculture supernatant (Abbott Laboratories), as well as by observation forany cytopathic effect (CPE) present in the cultures. When p24 antigenlevels were positive, the viral supernatant was harvested for theproceeding passage. Following each passage, the drug concentrations inthe subsequent passage were gradually increased. After 5 months ofselection, 1.5 μM of ABT-378 can be used in the final passage. The A17virus was generated after 17 passages of pNL4-3 in the presence ofABT-378 and ritonavir at concentration ratio of 5:1.

When tested by the above method, compounds of the present inventionexhibit EC₅₀ in the range of 1 nM to 1 μM.

Synthetic Methods

Abbreviations which have been used in the descriptions of the scheme andthe examples that follow are: DMF is N,N-dimethylformamide, DMSO isdimethylsulfoxide, THF is tetrahydrofuran, NMMO is 4-methylmorpholineN-oxide, HOBT is 1-hydroxybenzotriazole hydrate, DCC is1,3-dicyclohexylcarbodiimide, EDAC is1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, DMAP is4-(dimethylamino)pyridine, TFA is trifluoroacetic acid, and DEPBT is3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one.

The compounds and processes of the present invention will be betterunderstood in connection with the following synthetic schemes whichillustrate the methods by which the compounds of the invention may beprepared. Starting materials can be obtained from commercial sources orprepared by well-established literature methods known to those ofordinary skill in the art. The groups A, R, R₁, R₂, R₃, R₄, R₅, R₆, R₇,R₈, R₉, R₁₀, R₁₁, R₁₂, R₁₃, R₁₄ and n are as defined above unlessotherwise noted below.

This invention is intended to encompass compounds having formula (I),(II), (III), (IV), (V), (VI) or (VII) when prepared by syntheticprocesses or by metabolic processes. Preparation of the compounds of theinvention by metabolic processes includes those occurring in the humanor animal body (in vivo) or processes occurring in vitro.

Compounds of the invention can be prepared according to the methodsdescribed in Schemes 1-5 as shown below.

Compounds of formula (I) wherein P₁ is an N-protecting group (forexample tert-butyloxycarbonyl or benzyloxycarbonyl), can be treated withan amine having formula R³NH_(z) (for example isobutylamine,cyclopentymethylamine, cyclobutylmethylamine, and the like) in analcoholic solvent such as, but not limited to, ethanol or methanol at atemperature of about 25° C. to about 80° C., to give compounds of theformula (2). Compounds of formula (2) can be deprotected with an acid(for example, trifluoroacetic acid, hydrochloric acid, methanesulfonicacid, toluenesulfonic acid, sulfuric acid, aluminum chloride and thelike) in an inert solvent (for example, dioxane, dichloromethane,chloroform, methanol, tetrahydrofuran, acetonitrile and the like) at atemperature from about 0° C. to about room temperature, to provide (3).

Treatment of compound (2) with sulfonyl chlorides of formula (4), suchas, but not limited to, 4-methoxybenzenesulfonyl chloride in thepresence of an organic amine base (for example, triethylamine,diisobutylethyl amine, pyridine, and the like), at a temperature ofabout 25° C. to about 80° C., in an inert solvent such as, but notlimited to, dichloromethane, diethyl ether, tetrahydrofuran, chloroform,N,N-dimethylformamide, and the like, or mixtures thereof, give compoundsof formula (5). Compounds of formula (5) can be deprotected to compoundsof formula (6) using the conditions for the transformation of (2) to(3).

Compounds of formula (6) wherein R₄ is 4-[hydroxyimino)methyl]phenyl canbe obtained by (a) treating compounds of formula (2) with4-(diacetoxymethyl)benzenesulfonyl chloride (7), (b) treating theproduct from step (a) with hydroxylamine, and (c) deprotection of thecorresponding oxime of formula (8).

Alternatively, compounds of formula (6) wherein R₄ is4-[hydroxyimino)methyl]phenyl can also be obtained by (a) treatingcompounds of formula (2) with 4-vinylbenzenesulfonyl chloride, (b)oxidation of the product of step (a) with an oxidizing agent such as,but not limited to, osmium tetroxide, in the presence of sodiummetaperiodate to give aldehydes of formula (10), (c) treating compoundsof formula (10) with hydroxylamine to give compounds of formula (8), and(d) deprotection of compounds of formula (8).

Amino acid esters of formula (11), wherein P₂ is lower alkyls (forexample methyl, ethyl, tert-butyl and the like), can be treated with asuitably protected aldehyde of formula (12) (for example, P₁₀ and P₁₁together with the nitrogen atom they are attached, form a phthalimidogroup) in the presence of a reducing agent under acidic conditions (forexample, in the presence of acetic acid or hydrochloric acid) in aninert solvent, or mixture of solvents, such as methyl sulfoxide,methanol, dichloromethane, and the like, at a temperature of about roomtemperature to about 50° C., to provide compounds of formula (13).Examples of the reducing agent include, but are not limited to, sodiumtriacetoxyborohydride, sodium borohydride, sodium cyanoborohydride, andBH₃-pyridine.

Removal of the phthalimido group can be achieved using hydrazine in asuitable solvent such as ethanol and the like, at a temperature of aboutroom temperature to about 100° C., to provide compounds of formula (14).

Compounds of formula (14) can be converted to compounds of formula (15)by (a) treating compounds of formula (14) with an aldehyde havingformula R₉CHO, optionally in the presence of a drying agent (forexample, magnesium sulfate, silica gel and the like) in an inertsolvent, or mixture of solvents, such as dichloromethane, benzene,toluene, methanol, ethanol, methyl sulfoxide, and the like, at atemperature from about room temperature to about 100° C., and (b)reacting the product of step (a) with a reducing agent at about roomtemperature. Examples of the reducing agent include, but are not limitedto, sodium triacetoxyborohydride, sodium borohydride, sodiumcyanoborohydride, and BH₃-pyridine.

The diamine of formula (15) can be treated with a carbonylating agent inan inert solvent, or mixture of solvents, such as dichloromethane, 1,2dichloroethane, toluene, acetonitrile, and the like, at a temperature ofabout room temperature to about 100° C., to provide compounds of formula(16). Examples of the carbonylating agent include, but not are limitedto, 4-nitrophenyl carbonate, phosphene, diphosgene, triphosgene,carbonyl diimidazole, disuccinimidyl carbonate.

Conversion of compounds of formula (16) to the corresponding acidshaving formula (17) can be achieved by acid hydrolysis (for exampleacetic acid, trifluoroacetic acid, toluenesulfonic acid, formic acid,hydrochloric acid and the like) or base hydrolysis (for example sodiumhydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, andthe like) in a solvent, or mixture of solvents such asN,N-dimethylformamide, toluene, benzene, dichloromethane, ethyl acetate,water, methanol and the like, at a temperature of about 0° C. to about100° C.

Amino acid esters having formula (11), wherein P₂ is lower alkyls (forexample, methyl, ethyl, tert-butyl and the like) can be treated withcompounds of formula R³⁰OC(O)CH₂X, wherein R³⁰ is lower alkyls and X isBr, Cl, or I, in an inert solvent, or mixture of solvents, such asN,N-dimethylformamide, dichloromethane, 1,2-dichloroethane,acetonitrile, toluene, benzene, diethyl ether and the like, at atemperature of about room temperature to about 50° C., to provide (18).

Compounds of formula (18) can be converted to compounds of formula (19)by (a) treating with chlorosulfonyl isocyanate (or compounds of formulaXSO₂NCO, wherein X is Br, Cl, or I, and the like) in an inert solvent,or mixture of solvents, such as dichloromethane, 1,2-dichloroethane,dioxane, toluene, N,N-dimethylformamide, tetrahydrofuran diethyl etherand the like, at a temperature of about −10° C. to about roomtemperature, and (b) treating the product of step (a) with water atabout room temperature. Alternatively, (18) can be reacted with acarbonylating agent such as, but not are limited to, 4-nitrophenylcarbonate, phosphene, diphosgene, triphosgene, carbonyl diimidazole,disuccinimidyl carbonate, followed by reaction with ammonia.

Cyclization of the compounds of formula (19) to provide compounds offormula (20) can be achieved be treating with an organic amine base suchas triethyl amine, diisopropylethyl amine, imidazole, pyridine,N-methylmorpholine and the like, or an inorganic base such as sodiumbicarbonate, sodium carbonate, cesium carbonate and the like, in aninert solvent, or mixture of solvents, such as methanol, ethanol,N,N-dimethylformamide, dioxane, xylene, tetrahydrofuran and the like, ata temperature of about room temperature to about 70° C.

Imides of formula (20) can be converted to compounds of formula (22) by(a) deprotonation with a base in an inert solvent, or mixture ofsolvents, such as dichloromethane, 1,2-dichloroethane, tetrahydrofuran,diethyl ether, tert-butyl methyl ether, and the like, at a temperatureof about −78 to about 0° C., and (b) treating product of step (a) withan alkyl halide of formula (21), wherein X is Cl, Br or I, at atemperature of about room temperature to about 100° C. Examples of thebase include, but are not limited to, sodium hydride, potassium hydride,lithium diisopropyl amide, lithium bis(trimethylsilyl)amide.

Alternatively, compounds of formula (20) can be converted to compoundsof formula (22) by treating with an alcohol having formula R₁₁CH₂OH, inthe presence of triphenylphosphine and diethyl azodicarboxylate, in aninert solvent such as dichloromethane, tetrahydrofuran, dioxane orN,N-dimethylformamide, at a temperature of about 0° C. to about 25° C.

Conversion of compounds of formula (22) can be converted to compounds offormula (23) using the conditions for the transformation of compounds offormula (16) to compounds of formula (17).

Amino acid esters having formula (11) wherein P₂ is lower alkyls (forexample, methyl, ethyl, tert-butyl and the like) can be treated withcompounds such as, but not limited to, bis-(4-nitrophenyl)carbonate inan inert solvent, or mixture of solvents, such as N,N-dimethylformamide,dichloromethane, 1,2-dichloroethane, acetonitrile, toluene, benzene,diethyl ether and the like at a temperature of about room temperature toabout 50° C., to provide (24).

Treatment of alkyl halides of formula (21) wherein X is Cl, Br or I,with an amine of formula R₁₂NH₂ at a temperature of about 0° C. to about50° C. in an open container or in a sealed vessel gives compounds offormula (26). Compounds of formula (26) is treated with (24) in an inertsolvent, or mixture of solvents, such as N,N-dimethylformamide,dichloromethane, 1,2-dichloroethane, acetonitrile, toluene, benzene,diethyl ether, and the like, at a temperature of about room temperatureto about 100° C., to provide compounds of formula (27).

Conversion of compounds of formula (2′7) to compounds of formula (2S)can be achieved by using the conditions for the transformation ofcompounds of formula (16) to compounds of formula (17).

Compounds of formula (6) can be reacted with carboxylic acids of formula(17) or (23), or the corresponding salts, and an activating agent,optionally in the presence of 1-hydroxy-7-azabenzotriazole (HOAT),1-hydroxybenzotriazole hydrate (HOBT) or3-hydroxy-1,2,3-benzotriazin-4(3H)-one (HOOBT), and optionally in thepresence of an inorganic base (for example, NaHCO₃, Na₂CO₃, KHCO₃,K₂CO₃, NaOH or KOH, and the like) in an inert solvent (for example, 1:1ethyl acetate/water or isopropyl acetate/water or toluene/water ortetrahydrofuran/water and the like) at about room temperature, or anorganic amine base (for example, imidazole, 1-methylimidazole,2-methylimidazole, 2-isopropylimidazole, 4-methylimidazole,4-nitroimidazole, pyridine, N,N-dimethylaminopyridine, 1,2,4-triazole,pyrrole, 3-methylpyrrole, triethylamine or N-methylmorpholine and thelike) in an inert solvent (for example, ethyl acetate, isopropylacetate, tetrahydrofuran, toluene, acetonitrile, N,N-dimethylformamide,dichloromethane and the like) at a temperature of about 0° C. to about50° C. to provide compounds of formula (30). Examples of the activatingagent include, but are not limited to, 1,1′-carbonyldiimidazole (CDI),1,3-dicyclohexylcarbodiimide (DCC), 1,3-diisopropylcarbodiimide,1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC),DEPBT (3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one), PyBOP(benzotriazole-1-yl-oxy-tris-pyrrolidinophosphoniumhexafluorophosphate), and 1,3-di-tert-butylcarbodiimide. Alternatively,a salt or an activated ester derivative of acid (17) or (23) (forexample, the acid chloride, prepared by reaction of the carboxylic acidwith thionyl chloride in ethyl acetate or tetrahydrofuran or oxalylchloride in toluene/N,N-dimethylformamide) can be reacted with (6).

Alternatively, compounds of formula (30) can be obtained by (a) treatingcompounds of formula (3) with compounds of formula (17) using theconditions for the transformation of compound of formula (6) to (30),and (b) treating the product from step (a) with a compound havingformula R₄SO₂Cl, using the conditions for the transformation ofcompounds of formula (2) to compounds of formula (5).

Compounds of formula (6) can also be coupled to acids having formula(2S) using the coupling conditions for the transformation of compoundsof formula (6) to (30).

The present invention will now be described in connection with certainpreferred embodiments which are not intended to limit its scope. On thecontrary, the present invention covers all alternatives, modifications,and equivalents as can be included within the scope of the claims. Thus,the following examples, which include preferred embodiments, willillustrate the preferred practice of the present invention, it beingunderstood that the examples are for the purpose of illustration ofcertain preferred embodiments and are presented to provide what isbelieved to be the most useful and readily understood description of itsprocedures and conceptual aspects.

It will be understood that the term “purification” used hereinafter,unless otherwise stated, means column chromatography using a silica gelcolumn and eluting the column with a solvent system as specified in theexperimental details.

Compounds of the invention were named by ACD/ChemSketch version 4.01(developed by Advanced Chemistry Development, Inc., Toronto, ON, Canada)or were given names consistent with ACD nomenclature.

Example 1tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propylcarbamate

To a solution of(2R,3S)-3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (10 g) in2-propanol (100 mL) was added isobutylamine (11.4 mL, 3 equivalents),and the mixture was heated at 80° C. for 2.5 hours. After evaporation ofthe solvents, 11.86 g (93%) of the amine was produced in pure enoughform for use in the next step. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.90 (d,J=1.47 Hz, 3H), 0.92 (d, J=1.47 Hz, 3H), 1.35 (s, 9H), 1.59 (s, 1H),1.70 (m, 1H), 2.41 (d, J=6.99 Hz, 2H), 2.68 (d, J=4.78 Hz, 2H), 2.88 (d,J=8.09 Hz, 1H), 2.97 (d, J=4.41 Hz, 1H), 3.01 (d, J=4.78 Hz, 1H), 3.45(q, J=5.52 Hz, 1H), 3.80 (s, 1H), 4.68 (d, J=8.09 Hz, 1H), 7.21 (m, 3H),7.29 (m, 2H).

The compounds listed in Table 1, wherein X₃ represents the point ofattachment to the core structure (A), were prepared by the procedure ofExample 1.

TABLE 1 (A)

Ex. R₃ 2

3

4

5

6

7

8

9

10

11

12

13

14

15

Example 16tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-vinylphenyl)sulfonyl]amino}propylcarbamate

To a solution of Example 1 (11.86 g) in dichloromethane (100 mL) wasadded triethylamine (TEA) (19.6 mL, 4 equivalents) followed by dropwiseaddition of vinylbenzenesulfonyl chloride (8.36 g, 1.2 equivalents) at25° C. for 3 hrs. The mixture was partitioned in 1N sodium bicarbonate(NaHCO₃) and ethyl acetate (EtOAc). The organic extract wasconcentrated, and the residue was chromatographed on silica gel, elutingwith ethyl acetate/hexanes (1:4) to afford the title compound (9.6 g,54%). ¹H NMR (300 MHz, CDCl₃): δ ppm 0.87 (d, J=6.44 Hz, 3H), 0.90 (d,J=6.78 Hz, 3H), 1.34 (s, 9H), 1.86 (m, 1H), 2.84 (dd, J=13.39, 6.61 Hz,2H), 2.97 (m, 3H), 3.11 (m, 3H), 3.79 (s, 1H), 4.61 (s, 1H), 5.44 (d,J=10.85 Hz, 1H), 5.88 (d, J=17.63 Hz, 1H), 6.75 (dd, J=17.63, 10.85 Hz,1H), 7.25 (m, 5H), 7.51 (d, J=8.48 Hz, 2H), 7.72 (d, J=8.48 Hz, 2H).

Example 17tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamateMethod A Part 1tert-butyl(1S,2R)-1-benzyl-3-[[(4-formylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropylcarbamate

To Example 16 (8 g) in 80% tetrahydrofuran/water (120 mL) at 25° C. wasadded OsO₄ solution (2.9 mL, 4% by weight in water) followed by sodiumperiodate (6.76 g 2 equivalents). The mixture was stirred at 25° C. for16 hrs, quenched with 10% sodium thiosulfate solution, and extractedwith ethyl acetate. The organic extract was concentrated, and theresidue was chromatographed on silica gel, eluting with 3%methanol/dichloromethane to give the title compound (7 g, 87%).

Part 2tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate

A solution of hydroxylamine hydrochloride (2.08 g) in methanol (20 mL)was treated with a solution of KOH (1.68 g, 1 equivalent) in methanol(10 mL) at 0° C., stirred for 30 min, and filtered to give a 1 Msolution of hydroxylamine. This solution (15 mL, 1.5 equivalents) wasadded to a solution of the product of Part 1 of method A (7 g) inmethanol (25 mL), at 25° C. and stirred for 1 h. The reaction mixturewas partitioned between ethyl acetate and brine. The organic extract wasconcentrated. The residue was chromatographed on silica gel using 5%methanol/CHCl₃. A second purification was performed using 15% ethylacetate in dichloromethane to give the product (6.85 g, 95%).

Method B Part 1 (acetyloxy)[4-(chlorosulfonyl)phenyl]methyl acetate

A solution of p-toluenesulfonyl chloride (40.2 g) in acetic acid:aceticanhydride (800 mL, 1:1) was treated with conc. sulfuric acid (64 mL, 5equivalents) at 0-5° C. Chromium trioxide (80 g, 4 equivalents) wasadded at such a rate that the temperature remained below 10° C. Themixture was stirred at 5-10° C. until reaction was completed asindicated by TLC. The mixture was quenched with ice water (2 L), and thesolids were filtered, washed with water, and dried. The solids werecombined with saturated NaHCO₃ (1 L) at 25° C. for 2 hrs, filtered,dissolved in dichloromethane (1 L), dried over Na₂SO₄, filtered andconcentrated. The residue was recrystallized from 2-3 volumes of hotacetone/pentane and cooling for 16 hrs. The crystals are filtered, andwashed with cold pentane to give the product (24 g, 38%). ¹H NMR(CDCl₃): δ 8.09 (d, J=9 Hz, 2H), 7.77 (d, J=9 Hz, 2H), 7.73 (s, 1H),2.16 (s, 6H).

Part 2(acetyloxy)(4-{[{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}(isobutyl)amino]sulfonyl}phenyl)methylacetate

A solution of Example 1 (12.82 g) in tetrahydrofuran (95 mL) was treatedwith triethylamine (15.9 mL), followed by a solution of the product ofPart 1 of method B (14.0 g) in tetrahydrofuran (95 mL) and stirred at25° C. for 4 hrs. The mixture was treated with saturated NaHCO₃ solution(125 mL), and the solvents were evaporated. The residue was diluted withwater and extracted with ethyl acetate (3×), and the combined organiclayers were dried over Na₂SO₄, filtered and concentrated to give theproduct.

Part 3tert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate

A solution of the product of Part 2 of method B (23.1 g) in ethanol (254mL) was treated sequentially with hydroxylamine hydrochloride (5.29 g)and triethylamine (21.2 mL), stirred at 75° C. for 4 hrs, cooled to 25°C., and concentrated. The residue was diluted with ethyl acetate andwashed sequentially with water (3×) and saturated NaCl solution. Theorganic layer was separated, and concentrated. The solids formed wasrecrystallized by addition of about 2-3 volumes (relative to solid) ofboiling ethyl acetate, followed by hexanes (2-3 volumes relative toethyl acetate) until crystallization began. The mixture was kept at 25°C. for 18 h, and the solids were filtered and washed with hexanes togive the product (14.38 g, 73%). ¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (d,J=6.44 Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 1.35 (s, 9H), 1.85 (m, 1H),2.95 (m, 2H), 2.94 (s, 1H), 3.13 (m, 2H), 3.80 (s, 2H), 3.87 (s, 1H),4.63 (d, J=5.76 Hz, 1H), 7.25 (m, 5H), 7.70 (d, J=8.48 Hz, 2H), 7.78 (d,J=8.48 Hz, 2H), 8.16 (s, 1H).

Example 18N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-[(E)-(hydroxyimino)methyl]-N-isobutylbenzenesulfonamide

A solution of Example 17 in dichloromethane (60 mL) was treated with 80%trifluoroacetic acid at 0° C. for 3 h. The solvents were evaporated, andthe cis and trans oximes were treated with 5% trifluoroacetic acid indichloromethane (20 mL) at 25° C. for 16 h. The solvents wereevaporated, and the residue was partitioned between ethyl acetate and 1NNaHCO₃. After evaporating the solvents, the residue was filtered througha silica gel plug using 5% methanol in ethyl acetate (1% NH₄OH) andre-evaporated to give 3.62 g (91%). The trans isomer was separated fromthe cis by repeatedly crystallizing the solids from 5% methanol in ethylacetate (50 mL). Approximately 3 g of pure trans isomer was recoveredafter six recrystallizations.

The compounds listed in Table 2 wherein X₃ represents the point ofattachment to the core structure (B) were prepared by method A or methodB as exemplified in Example 17 and Example 18.

TABLE 2 (B)

Ex Met. R₃ Ex Method R₃ Ex Mehod R₃ 19 A

20 B

21 B

22 B

23 B

24 B

25 B

26 A

27 A

28 B

29 A

30 B

31 B

Example 32(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoicacid Example 32A (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetaldehyde

To a solution of phthalimide diethylacetal (15 g) in tetrahydrofuran(THF) (30 mL) was added 10% aqueous HCl (18 mL). After heating at 75° C.for 5 hrs, the solution was allowed to cool to RT, and ethyl acetate(100 mL) was added. The solution was extracted with saturated sodiumcarbonate solution (100 mL), brine (100 mL), and the organic layer wasseparated and dried over magnesium sulfate (MgSO₄). The solution wasfiltered and evaporated to provide 11.2 g of the titled compound.

Example 32B tert-butyl(2S,3S)-2-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]amino}-3-methylpentanoate

To a solution of Example 32A (12.1 g) in methanol (20 mL) was addedL-isoleucine tert-butyl ester hydrochloride (13.0 g, 58 mmol), sodiumcyanoborohydride (7.3 g, 116 mmol), and acetic acid (2 mL). Theresulting solution was stirred for 3 hrs at 25° C. and the methanolremoved under vacuum, dichloromethane (500 mL) added, and the solutionextracted with aq. NaHCO₃ (2×300 mL). Evaporation and purification ofthe organic layer gave 12.9 g of the title compound.

Example 32C tert-butyl(2S,3S)-2-[(2-aminoethyl)amino]-3-methylpentanoate

To a solution of Example 32B (12.9 g) in ethanol (400 mL) was addedhydrazine hydrate (11.2 mL). The solution was then heated to 70° C. for2 hrs. After cooling to 25° C., the resulting solid was dissolved in 1NNaOH solution (200 mL) and water (200 mL). The solution was thenextracted with dichloromethane (3×200 mL), the organic extractscombined, dried and evaporated to provide 6.8 g of the title compound.

Example 32D tert-butyl(2S,3S)-3-methyl-2-[(2-{[(6-methyl-2-pyridinyl)methyl]amino}ethyl)amino]pentanoate

6-Methyl-2-pyridinecarboxaldehyde (4.25 g) was dissolved indichloromethane (80 mL) and combined with Example 32C (8 g, 1equivalent) and MgSO₄ (15 g), and the mixture was stirred at 25° C. for2.5 hrs. The mixture was filtered, rinsed with dichloromethane, and thesolvents were evaporated. The residue was dissolved in methanol (80 mL)and treated with NaBH₄ at 0° C. for 0.5 h. The solvents were evaporated,and the residue was partitioned between saturated NaHCO₃ and ethylacetate. The organic layer was separated, washed with brine, dried overNa₂SO₄, and the solvents were evaporated to give 11 g of the titlecompound.

Example 32E tert-butyl(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoate

A solution of the product of Example 32D in N,N-dimethylformamide (60mL) was treated with bis-(p-nitrophenyl)carbonate (12.6 g, 1.2equivalents) at 50° C. for 5 hrs. The solvents were evaporated, and theresidue was partitioned between water and ethyl acetate. The organiclayer was separated, washed with brine, dried over Na₂SO₄, filtered, andthe solvents were evaporated, and the residue was purified using ethylacetate:hexanes (2:1) to give 7.3 g (57%) of the title compound.

Example 32F(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanoicacid

A solution of the product of Example 32E (7.3 g) in dichloromethane (50mL) and trifluoroacetic acid (50 mL) and the mixture was stirred at 25°C. for 3.5 hrs. The solvents were evaporated and the crude acid was useddirectly without purification.

The compounds listed in Table 3, wherein X₇ and X₉ represents the pointsof connection to the core structure (C), were prepared by the proceduresas exemplified in Examples 32A-32F, substituting the correspondingaldehydes to 6-methyl-2-pyridinecarboxaldehyde, and substituting thecorresponding amino acid esters or the salts of the amino acid estersfor L-isoleucine tert-butyl ester hydrochloride.

TABLE 3 (C)

Ex. R₉ R₇ 33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

Example 143(2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanoicacid Example 143A 2-{[(2-methyl-1,3-thiazol-4-yl)methyl]amino}ethanol

2-Methyl-4-(chloromethyl)thiazole (2.24 g) was treated with ethanolamine(11.6 mL, 10 equivalents) in dichloromethane at 25° C. for 16 hrs. Thesolvent was evaporated and the residue partitioned between ethyl acetateand brine. The organic layer was separated and extracted with ethylacetate (5×). The organic layers were combined and washed with brine,dried over Na₂SO₄, and the solvents were evaporated to give 2.4 g (85%)of title compound.

Example 143B tert-butyl2-hydroxyethyl[(2-methyl-1,3-thiazol-4-yl)methyl]carbamate

The product of Example 143A (2.4 g) was treated with di-t-butyldicarbonate (2.85 g, 1 equivalent) in tetrahydrofuran/1M NaHCO₃ (2:1)and stirred at 25° C. for 16 hrs. The solvents were evaporated, and theresidue was acidified with 10% citric acid and extracted with ethylacetate (3×). The combined organic layer was washed with brine, driedover Na₂SO₄ and evaporated. The crude product was purified using 1%methanol/dichloromethane to give 1.91 g (52%) of title compound.

Example 143Cmethyl(2S)-3-methyl-2-[(2-{[(2-methyl-1,3-thiazol-4-yl)methyl]amino}ethyl)amino]butanoate

A solution of the product of Example 143B (2.26 g) in dichloromethane(20 mL) was treated with oxalyl chloride (5.4 mL, 1.5 equivalents) at−78° C., and stirred for 15 min. DMSO (1.02 mL, 2 equivalents) was addeddropwise at −78° C., stirred for 15 min, and quenched with triethylamine(4 mL, 4 equivalents) as the mixture warmed to 0° C. The mixture wasquenched with 20% KH₂PO₄, and partitioned between dichloromethane andwater. The organic layer was washed with brine, dried over Na₂SO₄,filtered, and the solvents were evaporated. To this crude product wasadded methanol/water (7:2), (L)-valine methyl ester (1.21 g, 1equivalent), sodium acetate trihydrate (1.96 g, 2 equivalents), andNaCNBH₃ (0.95 g, 2 equivalents) was added portionwise over 30 min. Afterstirring for 1 hour the mixture was partitioned between saturated NaHCO₃and extracted with ethyl acetate (2×). The combined organic layer waswashed with brine, dried with Na₂SO₄, and evaporated. The residue wastreated with dichloromethane/trifluoacetic acid (10 mL, 1:1) and stirredat 25° C. for 2 hrs and concentrated.

Example 143D(2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoicacid

A solution of the product of Example 143C (5.4 g) in tetrahydrofuran (80mL) was treated with carbonydiimidazole (6.1 g, 2 equivalents) at 25° C.for 2 hrs. The mixture was quenched with 10% citric acid, the organiclayer was separated, washed with water, brine, dried over Na₂SO₄,filtered, and the solvents were evaporated A solution of the residue(3.3 g) in dioxane (20 mL) was treated with 1M LiOH (20 mL) at 25° C.for 2 hrs. The solvents were evaporated, and the residue was acidifiedwith 10% HCl, extracted with dichloromethane/2-propanol (3:1), theorganic layer was separated, dried over Na₂SO₄, filtered, and thesolvents evaporated to give 1.5 g of the title compound.

The compounds listed in Table 4, wherein X₇ and X₉ represents the pointsof connection to the core structure (C), were prepared by the proceduresas exemplified in Examples 143A-143D, substituting the correspondinghalides for 2-methyl-4-(chloromethyl)thiazole, and substituting thecorresponding amino acid esters for (L)-valine methyl ester.

TABLE 4 Ex. R₉ R₇ 144

145

146

147

Example 148(2S)-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxoimidazolidin-1-yl}butanoicacid Example 148AN-(2,2-dimethoxyethyl)-N-[(1-methyl-1H-benzimidazol-2-yl)methyl]amine

A solution of 1-methyl-2-formylbenzimidazole (1 g) in methanol (27 mL)and acetic acid (0.54 mL) was treated with aminoacetaldehydediethylacetal (0.9 g, 1 equivalent) and NaCNBH₃ (0.85 g, 2 equivalents)at 25° C., stirred for 1 hour. The mixture was partitioned between waterand ethyl acetate. The organic layer was separated, washed sequentiallywith saturated NaHCO₃ and brine, and concentrated. The residue waschromatographed on silica gel, eluting with 8% methanol/dichloromethaneto give 1.2 g (64%) of the title compound.

Example 148B 9H-fluoren-9-ylmethyl2,2-dimethoxyethyl[(1-methyl-1H-benzimidazol-2-yl)methyl]carbamate

A solution of the product of Example 148A (1.2 g) in dichloromethane (30mL) was treated with 9-fluorenylmethyl succinimide (1.6 g, 1.05equivalents) at 0° C. for 16 hours. The mixture was partitioned betweenwater and ethyl acetate. The organic layer was separated, washedsequentially with 10% NaHCO₃ and brine, dried over Na₂SO₄, filtered andconcentrated. The residue was chromatographed on silica gel, elutingwith ethyl acetate:dichloromethane (1:1) to give 1.83 g (84%) of thetitle compound.

Example 148C9H-fluoren-9-ylmethyl(1-methyl-1H-benzimidazol-2-yl)methyl(2-oxoethyl)carbamate

A solution of the product of Example 148B (0.2 g) in tetrahydrofuran(0.2 mL) was treated with 30% HCl (0.2 mL), stirred at 75° C. for 6hours, cooled to 25′C and concentrated. The residue was partitionedbetween 10% NaHCO₃ and ethyl acetate, the organic layer was separatedand washed with brine, dried over Na₂SO₄, filtered and concentrated togive the title compound (175 mg).

Example 148Dmethyl(2S)-2-[(2-{[(9H-fluoren-9-ylmethoxy)carbonyl][(1-methyl-1H-benzimidazol-2-yl)methyl]amino}ethyl)amino]-3,3-dimethylbutanoate

A solution of the product of Example 148C (0.178 g) and (L)-methylt-leucinate hydrochloride (76.1 mg, 1 equivalent) in methanol (1.7 mL)and acetic acid (17 μL) was treated with NaCNBH₃ (54 mg, 2 equivalents)at 25° C. for 3.5 hours. The mixture was partitioned between water andethyl acetate. The organic layer was separated and washed with 1N NaHCO₃and brine, and concentrated. The residue was chromatographed on silicagel, eluting with ethyl acetate:dichloromethane (3:1) to give 0.19 g(83%) of the title compound.

Example 148Emethyl(2S)-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxoimidazolidin-1-yl}butanoate

A solution of the product of Example 148D (0.19 g) inN,N-dimethylformamide (3.5 mL) was treated with diethylamine (0.35 mL),stirred at 25° C. for 1.5 hours and concentrated. A solution of theresidue in dichloroethane (7 mL) was treated with bis-(p-nitrophenyl)carbonate (0.128 g, 1.2 equivalents), stirred at 60° C. for 16 hours andconcentrated. The residue was chromatographed on silica gel, elutingwith ethyl acetate:dichloromethane (3:2) to give 80 mg (64%) of thetitle compound.

Example 148F(2S)-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxoimidazolidin-1-yl}butanoicacid

A solution of the product of Example 148E (37 mg) in tetrahydrofuran(0.26 mL) and water (0.13 mL) was treated with LiOH (6.1 mg, 1.4equivalents), stirred at 25° C. for 16 hours, quenched with 1N HCl (0.15mL) at 0° C., and the solvents were evaporated to give the crude productto be used without further purification.

The compounds listed in Table 5, wherein X₇ and X₉ representrespectively the points of connection to the core structure (C), wereprepared by the procedures as exemplified in Example 148A-148F,substituting the corresponding aldehydes for1-methyl-2-formylbenzimidazole, and substituting the corresponding aminoacid esters for (L)-methyl t-leucinate hydrochloride.

TABLE 5 Ex. R₉ R₇ 149

150

151

152

153

154

155

156

157

158

Example 159(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanoicacid Example 159A tert-butyl(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanoate

Example 273D (0.2 g, 0.54 mmol) was dissolved in toluene:ethanol (2.2mL, 1:1) and treated with dimethylamine (0.54 mL, 2M in tetrahydrofuran,2 equivalents) at 70° C. for 3 h. The mixture was cooled to 25° C. andtreated with sodium borohydride (20 mg, 3 equivalents) at 25° C. for 68h. The solvents were evaporated, and the crude residue was partitionedbetween ethyl acetate and saturated sodium bicarbonate. The organiclayer was separated, washed with brine, dried over magnesium sulfate,and the solvents were evaporated. The crude residue was purified usingethyl acetate-ethyl acetate/10% methanol to give 0.11 g (53%) of thetitle compound.

Example 159B(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanoicacid

Example 159A was dissolved in dichloromethane:trifluoroacetic acid (2.4mL, 1:1) at 25° C. for 1 h. The solvents were evaporated to give thetitle compound used directly for the next step.

Example 160(2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-imidazol-1-yl}butanoicacid Example 160AN-(2,2-diethoxyethyl)-N-[(2-methyl-1,3-thiazol-4-yl)methyl]amine

4-Chloromethyl-2-methylthiazole (0.6 g, 4 mmol) was added toaminoacetaldehyde diethyl acetal (5 mL, 10 equivalents) dissolved intetrahydrofuran (15 mL) at 25° C., and the mixture was stirred for 16 h.The solvents were evaporated and the excess aldehyde was distilled fromthe crude mixture. The crude residue was purified usingdichloromethane—dichloromethane/10% methanol to give 0.76 g (76%) of thetitle compound.

Example 160Bmethyl(2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-imidazol-1-yl}butanoate

Example 160A (0.76 g, 3.1 mmol) was dissolved in tetrahydrofuran (12 mL)and treated with (L)-methyl valinate p-nitrophenylcarbamate (0.92 g, 1equivalent), triethylamine (0.43 mL, 2 equivalents), and DMAP (60 mg,1.5 equivalents) at 25° C. for 2 days. The solvents were evaporated, andthe crude residue was partitioned between ethyl acetate/10% sodiumcarbonate, the organic layer was separated, dried over magnesiumsulfate, and the solvents were evaporated. The crude material wasdissolved in formic acid (30 mL) at 25° C. for 16 h. the solvents wereevaporated and the crude residue was purified usingdichloromethane-ethyl acetate to give 0.51 g (53%) of the titlecompound.

Example 160C

Example 160B (0.1 g, 0.32 mmol) was dissolved in tetrahydrofuran:water(1.5 mL, 2:1) and treated with lithium hydroxide (40 mg, 3 equivalents)at 25° C. for 30 min. The mixture was combined with 1N HCl (1 mL) andpartitioned between ethyl acetate and brine. The organic layer wasseparated and dried over magnesium sulfate, and the solvents wereevaporated to give 95 mg (100%) of the title compound.

Example 161(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxoimidazolidin-1-yl)-3-methylbutanamideMethod A

Example 146 (62 mg) was combined with HOBT (39 mg, 1.5 equivalents) andEDAC (55 mg, 1.5 equivalents) in N,N-dimethylformamide (3 mL) andstirred for 1 h at 25° C. To this mixture was added N-methylmorpholine(MAIM) (42 μL, 2 equivalents) and Example 18 (80 mg, 1 equivalent). Themixture was stirred for 16 hrs, evaporated under vacuum, and purifiedusing 3% methanol/dichloromethane to give 54 mg (39%) of the titlecompound. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82(d, J=6.44 Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H),1.85 (m, 1H), 2.15 (m, 1H), 3.00 (m, 10H), 3.49 (s, 3H), 3.64 (d,J=10.85 Hz, 1H), 3.79 (m, 1H), 4.17 (m, 1H), 4.41 (d, J=15.26 Hz, 1H),4.51 (d, J=15.26 Hz, 1H), 4.71 (s, 2H), 6.51 (d, J=8.48 Hz, 1H), 7.11(s, 1H), 7.17 (m, 5H), 7.70 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),8.15 (s, 1H).

Example 162(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethyl-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxoimidazolidin-1-yl}butanamideMethod B

Example 148F (36 mg) was dissolved in N,N-dimethylformamide (1.0 mL) andtreated with Example 18 (44 mg, 1 equivalent), HOBT (14.4 mg, 1equivalent), N-methylmorpholine (57 μL, 5 equivalents), andbenzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate(PyBOP) (54.6 mg, 1 equivalent) at 25° C. for 16 hrs. The solvents wereevaporated, and the residue was purified using 9%methanol/dichloromethane to give 48 mg (62%) of the title compound. ¹HNMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz,3H), 0.94 (s, 9H), 1.90 (m, 1H), 2.75 (m, 2H), 2.90 (m, 1H), 3.09 (m,7H), 3.30 (dd, J=8.99, 4.92 Hz, 1H), 3.81 (s, 3H), 3.85 (m, 1H), 4.05(m, 1H), 4.67 (d, J=15.26 Hz, 1H), 4.86 (d, J=15.26 Hz, 1H), 6.20 (d,J=8.48 Hz, 1H), 7.12 (m, 5H), 7.32 (m, 3H), 7.75 (m, 5H), 8.19 (s, 1H).

The compounds listed in Table 6, wherein X₃, X₇ and X₉ representrespectively the points of connection to the core structure (D), wereprepared by coupling the corresponding acids (Examples 32-160) with thecorresponding amines (Examples 1-31) using procedure exemplified byExample 161 (method A) and Example 162 (method B).

TABLE 6 (D)

Cpd # Method R₉ R₇ R₃ 163 A

164 A

165 A

166 A

167 A

168 A

169 A

170 A

171 A

172 A

173 A

174 A

175 A

176 B

177 A

178 A

179 A

180 A

181 A

182 A

183 A

184 A

185 A

186 A

187 A

188 A

189 A

190 A

191 B

192 A

193 A

194 A

195 A

196 A

197 A

198 A

199 A

200 B

201 A

202 A

203 B

204 B

205 B

206 A

207 A

208 A

209 A

210 A

211 A

212 A

213 B

214 B

215 A

216 B

217 B

218 A

219 A

220 A

221 A

222 A

223 A

224 A

225 A

226 A

227 B

228 B

229 A

230 A

231 A

232 A

233 A

234 B

235 A

236 A

237 A

238 B

239 B

240 B

241 A

242 A

243 A

244 A

245 A

246 A

247 A

248 A

249 A

250 A

251 A

252 A

253 A

254 A

255 A

256 A

257 B

258 A

259 A

260 A

261 A

262 A

263 A

264 A

265 A

266 B

267 B

268 B

269 B

Example 270(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide

Example 756 (13 mg, 0.019 mmol) was dissolved in ethanol (0.5 mL) andtreated with hydroxylamine hydrochloride (3.9 mg, 3 equivalents) for 3hrs at 25° C. The solvents were evaporated, and the residue was purifiedusing 8% methanol/dichloromethane to give 5 mg (38%) of the titlecompound.

Example 271 (2,2-diethoxyethylidyne)-λ⁴-sulfanylamine

1,1-Diethoxyacetamide (10 g, 0.068 mol) was dissolved in tetrahydrofuran(250 mL) and treated with P₄S₁₀ (3 g, 0.1 eq) at 25° C. for 16 h. Thesolvents were evaporated and diluted with ethyl acetate and water. Theorganic layer was washed with saturated sodium bicarbonate, brine, driedover magnesium sulfate, and the solvents were evaporated to give 7.13 g(64%) of the crude product used directly for the next step.

Example 272 ethyl 2-(diethoxymethyl)-1,3-thiazole-4-carboxylate

Example 271 (7.13 g, 0.044 mol) was dissolved in ethanol (90 mL) andtreated with ethyl bromopyruvate (5.5 mL, 1 equivalent) and 3 Amolecular sieves (20 g) and the mixture was heated at 80° C. for 30 min.The mixture was filtered and the solvents were evaporated. The cruderesidue was partitioned between ethyl acetate and saturated sodiumbicarbonate. The organic layer was washed with brine and dried overmagnesium sulfate. The solvents were evaporated and the crude residuewas purified using dichloromethane with increasing amounts of ethylacetate up to 10% to give 9.5 g (84%) of the thiazole.

Example 273(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxoimidazolidin-1-yl]butanamideExample 273A [2-(diethoxymethyl)-1,3-thiazol-4-yl]methanol Example 273B2-(diethoxymethyl)-1,3-thiazole-4-carbaldehyde

Example 272 (7.8 g, 30 mmol) was dissolved in toluene (60 mL) andtreated with diisobutyl aluminum hydride (42 mL, 1.4 equivalents, 1M intoluene) at −78° C. for 45 min. The mixture was quenched with ethylacetate (50 mL) and warmed to 25° C. while adding sodium potassiumtartrate (10 mL, 10%) for 2 h. the mixture was extracted with ethylacetate, the organic layer was washed with brine, dried over magnesiumsulfate, and the solvents were evaporated. Two products were purifiedusing ethyl acetate:hexane (1:1) to give 0.8 g (10%) of Example 273A andthe remaining fractions consisted of crude Example 273B.

Example 273C tert-butyl(2S)-2-(3-{[2-(diethoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanoate

Example 273B (0.144 g, 0.57 mmol) was dissolved in benzene:ethanol (3mL, 1:1) treated with the valine analog of Example 32C (0.14 g, 1equivalent) and the mixture was heated to 70° C. for 1 h. The mixturewas cooled to 25° C. and treated with sodium borohydride (75 mg, 3equivalents) for 2 h. The mixture was partitioned between ethyl acetateand water, the organic layer was washed with saturated sodiumbicarbonate, dried over magnesium sulfate and the solvents wereevaporated. The crude residue was dissolved in dichloroethane (25 mL)and treated with bis-(p-nitrophenylcarbonate) (0.245 g, 1.2 equivalents)and heated to 60° C. for 16 h. The solvents were evaporated and thecrude residue was purified using dichloromethane (100%) to hexane (100%)to hexane:ethyl acetate (1:1) to give 0.115 g (39% for 4 steps) of thetitle compound.

Example 273D tert-butyl(2S)-2-{3-[(2-formyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanoate

Example 273C (0.1 g, 0.24 mmol) was dissolved in acetone (10 mL) andtreated with 1M HCl (1 mL) at 70° C. for 45 min. The solvents wereevaporated and the crude residue was partitioned between ethyl acetateand saturated sodium bicarbonate, dried over magnesium sulfate,filtered, and the solvents were evaporated to give 89 mg (99%) of thetitle compound.

Example 273E tert-butyl(2S)-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanoate

Example 273D (0.2 g, 0.54 mmol) was dissolved in toluene (1.1 mL) andethanol (1.1 mL) and treated with methylamine solution intetrahydrofuran (0.54 mL, 2M, 2 equivalents) and stirred at 70° C. for 3h. The mixture was cooled to 25° C. and combined with sodium borohydride(20 mg, 3 equivalents) and stirred for 18 h. The solvents wereevaporated, and the residue was partitioned between ethyl acetate andsaturated sodium bicarbonate. The organic layer separated, washed withbrine and dried over sodium sulfate. The solvents were evaporated andthe crude residue was purified using chloroform-95% chloroform/5%methanol to give 0.118 g (56%) of the title compound.

Example 273F tert-butyl(2S)-2-{3-[(2-{[[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanoate

Example 273E (0.115 g, 0.3 mmol) was dissolved in dichloromethane (3mL), cooled to 0° C., combined with triethylamine (90 μL, 2.2equivalents) and fluorenylmethyl chloroformate (86 mg, 1.1 equivalents).The mixture was stirred at 0° C. for 1 h, then at 25° C. for 18 h. Thesolvents were evaporated, and the crude residue was purified using ethylacetate:hexanes (1:1) to give 0.138 g (76%) of the title compound.

Example 273G9H-fluoren-9-ylmethyl{4-[(3-{(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylpropyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methyl(methyl)carbamate

Example 273F (10 mg, 0.017 mmol) was dissolved in trifluoroaceticacid:dichloromethane (1:1, 0.3 mL) at 25° C. for 90 min. The solventswere evaporated, and the crude residue was dissolved indimethylformamide (0.2 mL) and treated with N-methyl morpholine (3.4 mg,1.5 equivalents), HOBT (3.4 mg, 1.5 equivalents), EDAC (4.8 mg, 1.5equivalents), and Example 18 (10 mg, 1.5 equivalents). The mixture wasstirred at 25° C. for 68 h. The solvents were evaporated and the cruderesidue was purified using C-18 column to give 8 mg (51%) of the titlecompound.

Example 273H(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide

Example 273G (8 mg, 0.008 mmol) was dissolved in acetonitrile (0.1 mL)and treated with diethylamine (2 μL, 3 equivalents) at 25° C. for 1 h.The solvents were evaporated and the residue was purified using C-18 togive 6.5 mg (92%) of the title compound.

Example 274(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(pyrrolidin-2-ylmethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamideExample 274A (2R,3S)-3-amino-1-azido-4-phenylbutan-2-ol

A solution of(2R,3S)-3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (1.17 g)in ethanol:water (45 mL, 4:1) was treated with lithium azide (1.09 g, 5equivalents) and NH₄Cl (1.19 g, 5 equivalents), stirred at 75° C. for 2hours and concentrated. The residue was partitioned between water andethyl acetate. The organic layer was separated, dried over MgSO₄,filtered and concentrated. A solution of the residue indichloromethane/trifluoroacetic acid (40 mL, 1:1) was stirred at 25° C.for 1 hour and concentrated to give the title compound.

Example 274B(2S)—N-[(1S,2R)-3-azido-1-benzyl-2-hydroxypropyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide

A solution of the product of Example 274A (0.825 g) inN,N-dimethylformamide (30 mL) was treated with EDAC (0.744 g, 1.2equivalents), HOBT (0.65 g, 1.2 equivalents), N methyl morpholine (0.88mL, 2 equivalents) and Example 143D (1.19 g, 1 equivalent), stirred at25° C. for 1 hour and concentrated. The residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 1.3 g (67%) oftitle compound.

Example 274C(2S)—N-[(1S,2R)-3-amino-1-benzyl-2-hydroxypropyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide

A solution of the product of Example 274B (1.3 g) intetrahydrofuran:water (25 mL, 4:1) was treated with triphenylphosphine(1.4 g, 2 equivalents), stirred at 70° C. for 2 hours and concentrated.The residue was partitioned between 1N HCl and dichloromethane. Theaqueous layer was separated and made basic using 1N NaOH, extracted withdichloromethane and the organic extract was concentrated. The residuewas purified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give0.76 g (62%) of the title compound.

Example 274D tert-butyl2-[({(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanoyl)amino]-4-phenylbutyl}amino)methyl]pyrrolidine-1-carboxylate

A solution of the product of Example 274C (59 mg) in ethanol:benzene (1mL, 1:1) was treated with N-t-butoxylcarbonyl-(L)-prolinal (26 mg, 1equivalent), stirred at 70° C. for 1 hour, cooled at 25° C., treatedwith NaBH₄ (14 mg, 3 equivalents) at 25° C. and stirred for 16 hours.The mixture was quenched with saturated NH₄Cl and partitioned betweenwater and ethyl acetate. The organic layer was separated, dried overMgSO₄, filtered and concentrated to give 85 mg of the crude titlecompound.

Example 274E tert-butyl2-[(({4-[(hydroxyimino)methyl]phenyl}sulfonyl){(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanoyl)amino]-4-phenylbutyl}amino)methyl]pyrrolidine-1-carboxylate

A solution of the product of Example 274D (85 mg) in dichloromethane(0.6 mL) was treated with triethylamine (17 μL, 2 equivalents) and4-formylbenzenesulfonyl chloride (12 mg, 1 equivalent), stirred at 25°C. for 2 hours and concentrated. A solution of the residue in methanol(1 mL) was treated with hydroxylamine hydrochloride, stirred at 25° C.for 16 hours and concentrated. The residue was purified by HPLC reversephase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 16 mg (20% over3 steps) of the title compound.

Example 274F(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(pyrrolidin-2-ylmethyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamide

A solution of the product of Example 274E (12 mg) in dichloromethane(0.5 mL) and trifluoroacetic acid (0.5 mL) was stirred at 25° C. for 1hour and concentrated. The residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(95:5) to acetonitrile (100%) to give 10 mg (95%) of the title compound.

Example 275(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-2,3-dihydro-1H-imidazol-1-yl}butanamide

Example 160C (62 mg, 0.22 mmol) was combined with HOBT (43 mg, 1.5equivalents) and EDAC (60 mg, 1.5 equivalents) in N,N-dimethylformamide(3 mL) and stirred for 1 hour at 25° C. To this mixture was addedN-methyl morpholine (43 μL, 3 equivalents) Example 18 (88 mg, 1.1equivalents). The mixture was stirred for 16 hours, evaporated, andchromatographed, eluting with 2.5% methanol/dichloromethane to give 60mg (41%) of title compound.

Example 276(2S)-2-[3-(3-aminobenzyl)-2-oxoimidazolidin-1-yl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide

Example 174 (68 mg, 0.09 mmol) was dissolved in ethyl acetate (1 mL) wastreated with 10% Pd/C (14 mg) for 2 h. After work-up, the crude residuewas purified using 3% methanol/chloroform to give 53 mg (82%) of thetitle compound.

Example 277(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-oxido-3-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}pentanamide

Example 179 (14.8 mg) was dissolved in tetrahydrofuran (0.25 mL) andtreated with m-chloroperbenzoic acid (6 mg, 1.5 equivalents) at 25° C.for 3 h. The solvents were evaporated, and the residue was purifiedusing 7% methanol/dichloromethane to give 12.5 mg (83%) of the titlecompound.

Example 278(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(1-oxidopyridin-4-yl)methyl]-2-oxoimidazolidin-1-yl}pentanamide

Example 181 (10.4 mg) was dissolved in tetrahydrofuran (0.25 mL) andtreated with m-chloroperbenzoic acid (6 mg, 1.5 equivalents) at 25° C.for 3 h. The solvents were evaporated, and the residue was purifiedusing 7% methanol/dichloromethane to give 10.5 mg (98%) of the titlecompound.

Example 279(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxoimidazolidin-1-yl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamideExample 279Atert-butyl(2S,3S)-2-(3-{[2-(diethoxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanoate

Example 273B (0.86 g, 4 mmol) was dissolved in ethanol:benzene (12 mL,1:1) and treated with Example 32C (0.55 g, 2.4 mmol) at 70° C. for 1 h.The mixture is cooled to 25° C. and treated with sodium borohydride(0.275 g, 3 equivalents) for 2 h. The mixture is quenched with methanoland the solvents were evaporated. The crude residue was dissolved indichloroethane (100 mL) and treated with bis-p-nitrophenyl carbonate(0.9 g, 1.2 eq) at 70° C. for 16 h. The solvents were evaporated, andthe crude residue was partitioned between ethyl acetate and saturatedsodium bicarbonate, the organic layer was separated, washed with brine,dried over magnesium sulfate and the solvents were evaporated. The cruderesidue was purified using dichloromethane:hexanes(1:1)-hexanes-hexanes/ethyl acetate (1:1) to give 0.72 g (66%) of thetitle compound.

Example 279B tert-butyl(2S,3S)-2-{3-[(2-formyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanoate

Example 279A (0.72 g, 1.6 mmol) was dissolved in acetone (35 mL) andtreated with 1N HCl (3.5 mL) at 70° C. for 45 min. The solvents wereevaporated, and the residue was partitioned between ethyl acetate andsaturated sodium bicarbonate. The organic layer was separated and washedwith brine, dried over magnesium sulfate, and the solvents wereevaporated to give 0.584 g (97% crude) of the title compound.

Example 279C tert-butyl(2S,3S)-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanoate

Example 279B (0.2 g, 0.54 mmol) was dissolved in ethanol (5 mL) andtreated with sodium borohydride (30 mg, 1.5 equivalents) and stirred for2 h. The solvents were evaporated, and the residue was partitionedbetween ethyl acetate and water. The organic layer separated, washedwith brine and dried over magnesium sulfate. The solvents wereevaporated and the crude residue was used directly for the nextreaction.

Example 279D tert-butyl(2S,3S)-3-methyl-2-{3-[(2-{[(methylsulfonyl)oxy]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}pentanoate

Example 279C (0.2 g, 0.3 mmol) was dissolved in dichloromethane (5 mL),cooled to 0° C., combined with triethylamine (0.22 mL, 3 equivalents)and methanesulfonyl chloride (0.06 mL, 1.5 equivalents). The mixture wasstirred at 0° C. for 90 min. The solvents were evaporated, and the cruderesidue was diluted with ethyl acetate and washed with 10% citric acid,saturated sodium bicarbonate, brine, and dried over magnesium sulfate togive 0.25 g of crude Example 279D residue which was used directly forthe next reaction.

Example 279E tert-butyl(2S,3S)-2-(3-{[2-(azidomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanoate

Example 279D (0.25 g) was dissolved in dimethylformamide (4 mL) treatedwith lithium azide (0.255 g, 10 equivalents) and stirred at 50° C. for 1h. The solvents were evaporated and the residue was diluted withethylacetate and washed with water, brine, and dried over magnesiumsulfate. The solvents were evaporated to give 0.192 g crude azide.

Example 279F(2S,3S)-2-(3-{[2-({[(9H-fluoren-9-ylmethoxy)carbonyl]amino}methyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylpentanoicacid

Example 279E (0.19 g, 0.47 mmol) was dissolved in tetrahydrofuran (4 mL)and water (1 mL) and treated with triphenylphosphine (0.247 g, 2equivalents) and stirred at 50° C. for 1 h. The solvents were evaporatedand the crude residue (0.127 g) was dissolved in acetonitrile (2.5 mL)and water (0.7 mL) and treated with sodium bicarbonate (67 mg, 2.4equivalents) and fluorenylmethyl chloroformate (103 mg, 1.2 equivalents)and stirred at 25° C. for 90 min. The solvents were evaporated and thecrude residue was diluted with ethyl acetate and washed with water,brine, dried over magnesium sulfate, and filtered. The solvents wereevaporated and the crude residue was purified using chloroform:ethylacetate 4:1-1:1 to give 0.2 g (70%) of the ester. This ester wasdissolved in dichloromethane:trifluoroacetic acid (5 mL, 3:2) andstirred at 25° C. for 2 h. The solvents were evaporated to give 0.12 gof the title compound.

Example 279G(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[(2-{[(9H-fluoren-9-ylmethyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}-3-methylpentanamide

Example 279F (15 mg, 0.027 mmol) was dissolved in N,N-dimethylformamide(0.3 mL) and treated with EDAC (8 mg, 1.5 equivalents), HOBT (6 mg, 1.5equivalents), N-methyl morpholine (7 μL, 2.5 equivalents), followed byExample 18 (17 mg, 1.5 equivalents) at 25° C. for 16 hrs. The solventswere evaporated, and the residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(75:25) to acetonitrile (100%) to give 12.3 mg (46%) of the titlecompound.

Example 279H(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide

Example 279G (12 mg) was dissolved in acetonitrile (0.2 mL) and treatedwith diethylamine (3 μL, 3 equivalents) at 25° C. for 2 h. The solventswere evaporated, and the residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(75:25) to acetonitrile (100%) to give 9.8 mg (92%) of the titlecompound.

Example 280(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamideExample 280A9H-fluoren-9-ylmethyl{4-[(3-{(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methylcarbamate

In a similar manner to Example 279G, Example 280A was prepared usingExample 279F (15 mg, 0.027 mmol), N-methyl morpholine (7 μL, 2.5equivalents), HOBT (6 mg, 1.5 equivalents), EDAC (8 mg, 1.5 equivalents)and Example 19 (18 mg, 1.5 equivalents) in dimethylfomamide (0.3 mL) togive 11.8 mg (46%) after purification on C-18 using 75% water/0.1%trifluoroacetic acid/25% acetonitrile-100% acetonitrile.

Example 280B9H-fluoren-9-ylmethyl{4-[(3-{(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methylcarbamate

In a similar manner to Example 279H, Example 280A (11 mg, 0.013 mmol)was treated with diethylamine (3 μL). The crude product was purified byC-18 using 95% water/0.1% trifluoroacetic acid/5% acetonitrile-100%acetonitrile to give 7.8 mg (76%) of the title compound.

Example 281(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

In a similar manner to Example 280, Example 281 was prepared usingExample 279F (75 mg, 0.14 mmol), N-methyl morpholine (38 μL, 2.5equivalents), HOBT (28 mg, 1.5 equivalents), EDAC (39 mg, 1.5equivalents) and Example 27 (91 mg, 1.5 equivalents) in dimethylfomamide(1.2 mL) to give 79.5 mg (60%) after purification on C-18 using 75%water/0.1% trifluoroacetic acid/25% acetonitrile-100% acetonitrile. Thisproduct was treated with diethylamine (20 μL, 3 equivalents) as inExample 279H. The crude product was purified by C-18 using 95%water/0.1% trifluoroacetic acid/5% acetonitrile-100% acetonitrile togive 49 mg (70%) of the title compound.

Example 282(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]pyridin-4-yl}methyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-3-methylpentanamide

Example 405 (30 mg, 0.039 mmol) was dissolved in ethanol (1 mL) andtreated with NaBH₄ (7 mg, 5 equivalents) at 25° C. for 16 hrs. Themixture was partitioned between water and ethyl acetate. The organiclayer was separated, dried over NaSO₄, filtered and the solvents wereevaporated. The residue was dissolved in dichloromethane (1 mL) andtrifluoroacetic acid (1 mL) at 25° C. for 1 h and the mixture waspartitioned between water and ethyl acetate, the organic layer waswashed with saturated NaHCO₃, water, brine, and dried over NaSO₄,filtered and the solvents were evaporated. The residue was purifiedusing 7% methanol/dichloromethane to give 25.5 mg (88%) of the titlecompound.

Example 283(2R,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamideExample 283A tert-butyl(2S,3S)-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanoate

A solution of Example 273D (65 mg) in toluene:ethanol (0.7 mL, 1:1) wastreated with isopropylamine (0.14 mL, 10 equivalents), stirred at 70° C.in a capped vial for 2 hrs. The mixture was cooled to 25° C. and NaBH₄(19 mg, 3 equivalents) was added and the mixture was stirred at 25° C.for 3 days. The solvents were evaporated, and the residue waspartitioned between ethyl acetate and saturated NaHCO₃, the organiclayer was separated and washed with brine, dried over MgSO₄, filteredand evaporated to give 59 mg of the title compound.

Example 283B(2S,3S)-2-{3-[(2-{[[(9H-fluoren-9-ylmethoxy)carbonyl](isopropyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylpentanoicacid

A solution of the product of Example 283A (59 mg) in acetonitrile (0.9mL) and water (0.3 mL) was treated with NaHCO₃ (34 mg, 2.4 equivalents)followed by 9-fluorenylmethyl chloroformate (53 mg, 1.2 equivalents) at25° C. for 1.5 h. The solvents were evaporated and the residue waspurified using ethyl acetate:chloroform (1:4) to give 47 mg (40%) ofFMOC-amine which was dissolved in dichloromethane (0.5 mL) andtrifluoroacetic acid (0.5 mL) and stirred at 25° C. for 1 h. Thesolvents were evaporated, and the acid was used directly for the nextstep.

Example 283C9H-fluoren-9-ylmethyl{4-[(3-{(1S,2S)-1-[({(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}amino)carbonyl]-2-methylbutyl}-2-oxo-1-imidazolidinyl)methyl]-1,3-thiazol-2-yl}methyl(isopropyl)carbamate

A solution of crude Example 283B dissolved in N,N-dimethylformamide (0.6mL) was treated with EDAC (16 mg, 1.2 equivalents), HOBT (11 mg, 1.2equivalents) and N-methylmorpholine (18 μL, 2.4 equivalents) followed bythe Example 27 (36 mg, 1.2 equivalents) at 25° C. for 16 hrs. Thesolvents were evaporated, and the residue was purified using HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 38.5 mg (55%)of the title compound.

Example 283D(2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamideExample 284(2R,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-[3-({2-[(isopropylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylpentanamide

A solution of Example 283C (38.5 mg, 0.038 mmol) in acetonitrile (0.5mL) and diethylamine (9 μL, 3 equivalents) was stirred at 25° C. for 1h. The solvents were evaporated and the residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 30.9 mg ofamines. The two products were separated by preparative TLC using 0.5 mmsilica gel plates, eluting with 5% methanol/chloroform/0.2% ammoniumhydroxide to give 7.3 mg of Example 283D and 7.4 mg of Example 284.

Example 285(2S,3S)-2-(3-{3-[amino(hydroxyimino)methyl]benzyl}-2-oxo-1-imidazolidinyl)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide

Example 201 (65 mg) was dissolved in ethanol (1 mL) and treated withtriethylamine (0.13 mL, 10 equivalents) and hydroxylamine hydrochloride(25 mg, 4 equivalents) at 50° C. for 6 h. The mixture was partitionedbetween water and ethyl acetate, the organic layer was separated, driedover Na₂SO₄, filtered and the solvents were evaporated. The residue waspurified using 3% methanol/chloroform to give 57 mg (84%) of the titlecompound.

Example 286(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-{3-[3-(hydroxymethyl)benzyl]-2-oxo-1-imidazolidinyl}-3-methylpentanamideExample 286A 6-[(trityloxy)methyl]pyridine-2-carbaldehyde

2,6-Dimethanol pyridine (1 g) was prepared per J. Org. Chem. 63,3884-3894 (1998) to give 330 mg (12%) of the mono-trityl analog. Thetrityl ether (0.33 g) was dissolved in dichloromethane (2 mL) andstirred at 25° C. with manganese dioxide (0.5 g, 7 equivalents) for 3days. The mixture was filtered through Celite©, and purified usingdichloromethane to give 0.284 g (86%) of the title compound.

Example 286B tert-butyl(2S,3S)-3-methyl-2-[2-oxo-3-({6-[(trityloxy)methyl]pyridin-2-yl}methyl)imidazolidin-1-yl]pentanoate

A solution of the product of Example 286A (0.28 g) in dichloromethane (5mL) was treated with Example 32C (0.17 g, 1 equivalent) and MgSO₄ (1 g)and the mixture was stirred at 25° C. for 2 h. The mixture was filteredand the solvents were evaporated. The residue was dissolved in methanol(5 mL) and treated with NaBH₄ (42 mg, 1.5 equivalents) at 25° C. for 1h. The mixture was partitioned between water and ethyl acetate, theorganic layer was separated and dried over Na₂SO₄, filtered and thesolvents were evaporated. The residue was used directly for the nextstep. The crude diamine was dissolved in N,N-dimethylformamide (15 mL)and treated with bis-(p-nitrophenylcarbonate (0.27 g, 1.2 equivalents)at 50° C. for 3 h. The mixture was partitioned between water and ethylacetate and the organic layer was separated, washed with saturatedNaHCO₃, dried over NaSO₄, filtered and the solvents were evaporated. Theresidue was purified using 5% ethyl acetate in dichloromethane to give0.35 g (76%) of the title compound.

Example 286C(2S,3S)-3-methyl-2-[2-oxo-3-({6-[(trityloxy)methyl]pyridin-2-yl}methyl)imidazolidin-1-yl]pentanoicacid

A solution of the product of Example 286B (0.35 g) in trifluoroaceticacid:dichloromethane (3 mL, 2:1) was stirred at 25° C. for 2 hrs. Thesolvents were evaporated and the residue was directly used for the nextstep.

Example 286D(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[2-oxo-3-({6-[(trityloxy)methyl]pyridin-2-yl}methyl)imidazolidin-1-yl]pentanamide

A solution of the product of Example 286C (0.35 g, 0.59 mmol) inN,N-dimethylformamide (4 mL) was combined with EDAC (0.17 g, 1.5equivalents), HOBT (0.12 g, 1.5 equivalents), N-methylmorpholine (0.13mL, 2 equivalents) followed by the Example 18 (0.27 g, 1.1 equivalents).The mixture was stirred at 25° C. for 16 hrs and partitioned betweensaturated NaHCO₃ and ethyl acetate. The organic layer was separated anddried over Na₂SO₄, filtered and the solvents were evaporated. Theresidue was purified first using 2% methanol/chloroform followed byethyl acetate:hexanes (1:2) to give 0.243 g (43%) of the title compound.

Example 286E(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(hydroxymethyl)pyridin-2-yl]methyl}-2-oxoimidazolidin-1-yl)-3-methylpentanamide

A solution of the product of Example 286D (0.166 g) inmethanol:dichloromethane (2 mL, 3:2) at 0° C. was treated withconcentrated HCl (1 mL). The mixture was stirred at 25° C. for 30 minand partitioned into sat NaHCO₃ and dichloromethane. The organic layerwas separated and dried over NaSO₄, filtered, and the solvents wereevaporated. The residue was purified using 4% methanol/chloroform togive 69 mg (56%) of the title compound.

Example 287(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({6-[(hydroxyimino)methyl]-2-pyridinyl}methyl)-2-oxo-1-imidazolidinyl]-2,3-dimethylpentanamide

Example 286E (10 mg, 0.014 mmol) was dissolved in dichloromethane (50mL) and treated with MnO₂ (72 mg, 50 equivalents) at 25° C. for 16 hrs.Continue to add enough MnO₂ to complete the reaction. The mixture wasfiltered through Celite®, and the solvents were evaporated. The crudealdehyde was dissolved in methanol (1 mL) and treated with hydroxylaminehydrochloride (10 mg, 1.1 equivalents) at 25° C. for 1.5 h. The mixturewas partitioned between sat NaHCO₃ and ethyl acetate, the organic layerwas separated, dried over Na₂SO₄, filtered and the solvents wereevaporated. The residue was purified using ethyl acetate:hexanes (2:1)to give 1.7 mg (17%) of the title compound.

Example 288(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(1-hydroxyethyl)-2-pyridinyl]methyl}-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanamideExample 288A(2S)-2-{3-[(6-acetyl-2-pyridinyl)methyl]-2-oxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethylbutanamide

Example 122 (0.17 g) was dissolved in N,N-dimethylformamide (2 mL) andtreated with EDAC (0.19 g, 2.7 equivalents), HOBT (0.134 g, 2.7equivalents), N-methylmorpholine (88 μL, 2.1 equivalents) and Example 18(0.28 g, 1.78 equivalents) at 25° C. for 2.5 days. The mixture waspartitioned between 1N NaHCO₃ and ethyl acetate. The organic layer wasseparated, dried over Na₂SO₄, filtered and the solvents were evaporated.The residue was purified using ethyl acetate:hexanes (3:2) followed byusing 3% methanol/dichloromethane to give 99 mg (35%) of the titlecompound.

Example 288B(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[6-(1-hydroxyethyl)pyridin-2-yl]methyl}-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanamide

A solution of the product of Example 288A (86 mg) in methanol (1.5 mL)was treated with NaBH₄ (8.8 mg, 2 equivalents) at 0° C. The mixture wasstirred for 1 h at 25° C. and quenched by adding acetone (0.2 mL). Thesolvents were evaporated, and the residue was purified using 7%methanol/dichloromethane to give 83 mg (96%) of the title compound.

Example 289(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}pentanoicacid Example 289Atert-butyl(2S,3S)-2-[(2-ethoxy-2-oxoethyl)amino]-3-methylpentanoate

To a solution of (L)-iso-leucine tert-butyl ester hydrochloride (5 g,22.34 mmol) in N,N-dimethylformamide (30 mL) was added triethylamine(3.1 mL, 22.34 mmol), and the mixture was stirred for 1 h. The reactionwas filtered to remove solid salts, and the filtrate was treated withtriethylamine (9.3 mL, 67.0 mmol) and ethyl bromoacetate (9.9 mL, 67.0mmol), and the reaction was stirred for 3 h at 25° C. The reaction waspartitioned between ethyl acetate and water, and the organic was washedwith brine and dried over MgSO₄, filtered and evaporated to give 5.7 g(93%) of the product which was used without further purification.

Example 289B tert-butyl(2S,3S)-2-[(aminocarbonyl)(2-ethoxy-2-oxoethyl)amino]-3-methylpentanoate

To Example 289A (5.7 g, 20.9 mmol) in dichloromethane (60 mL) at 0° C.was added chlorosulfonyl isocyanate (2.7 mL, 31.0 mmol) and the mixturewas stirred at 0° C. for 16 h. Water (60 mL) was added to the coldreaction and the mixture was warmed to room temperature and stirred for4 h. The reaction was partitioned between dichloromethane and water, andthe organic was washed with brine and dried over MgSO₄, filtered andevaporated to give 6.83 g of the product which was used without furtherpurification.

Example 289C tert-butyl(2S,3S)-2-(2,4-dioxo-1-imidazolidinyl)-3-methylpentanoate

To Example 289B (6.8 g, 20.9 mmol) in methanol (30 mL) was addedtriethylamine (5.6 mL, 40.2 mmol), and the mixture was stirred at 50° C.for 2 h. The solvent was evaporated and the residue was chromatographedon silica gel eluting with a gradient starting with dichloromethane andending with 30% ethyl acetate in dichloromethane to give 2.53 g (47%) ofthe title compound

Example 289D tert-butyl(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}pentanoate

To Example 289C (0.107 g, 0.396 mmol) in dichloromethane (2 mL) at 0° C.were added 6-methyl-2-pyridinemethanol (0.053 mg, 0.435 mmol),triphenylphosphine (0.135 g, 0.515 mmol), followed by diethylazodicarboxylate (0.080 mL, 0.515 mmol), and the mixture was stirred atroom temperature for 16 h. Water (2 mL) was added and the reaction wasstirred for 2 h at room temperature. The reaction was partitionedbetween dichloromethane and water, and the organic was washed with brineand dried over MgSO₄, filtered and evaporated. The residue was purifiedusing a gradient starting with dichloromethane and ending with 30% ethylacetate in dichloromethane to give 0.154 g (94% yield) of the titlecompound.

Example 289E(2S,3S)-3-methyl-2-{3-[(6-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-imidazolidinyl}pentanoicacid

To Example 289D (0.154 g, 0.410 mmol) in dichloromethane (3 mL) wasadded trifluoracetic acid (3 mL), and the mixture was stirred at roomtemperature for 16 h. The solvent was evaporated and the product waspurified by reversed phase (C18) chromatography eluting with a gradientstarting with 5% acetonitrile in water (0.1% trifluoroacetic acid) andending with acetonitrile to give 0.153 g (93%) as the trifluoroaceticacid salt.

Example 290(2S)-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxol-imidazolidinyl}-3-methylbutanoicacid Example 290A tert-butyl(2S)-2-[(2-ethoxy-2-oxoethyl)amino]-3-methylbutanoate

To a solution of (L)-valine tert-butyl ester hydrochloride (4.94 g, 23.6mmol) in N,N-dimethylformamide (55 mL) was added triethylamine (3.28 mL,1 equivalent), and the mixture was stirred for 1 h. The reaction wasfiltered to remove solid salts, and the filtrate was treated withtriethylamine (9.85 mL, 3 equivalents) and ethyl bromoacetate (7.84 mL,3 equivalents), and the reaction was stirred for 3 h at 25° C. Thereaction was partitioned between ethyl acetate and water, and theorganic was washed with brine and dried over MgSO₄, filtered andevaporated to give 4.48 g (78%) of the product which was used withoutfurther purification.

Example 290B tert-butyl(2S)-2-[(aminocarbonyl)(2-ethoxy-2-oxoethyl)amino]-3-methylbutanoate

Example 290A (4.48 g, 18.3 mmol) was dissolved in dichloromethane (30mL) at 0° C. and was treated with chlorosulfonyl isocyanate (2.07 mL,1.3 equivalents) and the mixture was stirred at 0° C. for 16 h. Water(60 mL) was added to the cold reaction and the mixture was warmed to 25°C. and stirred for 4 h. The reaction was partitioned betweendichloromethane and water, and the organic was washed with brine anddried over MgSO₄, filtered and evaporated to give crude product whichwas used without further purification.

Example 290C tert-butyl(2S)-2-(2,4-dioxo-1-imidazolidinyl)-3-methylbutanoate

Example 290B (crude product) was dissolved in methanol (30 mL) and wastreated with triethylamine (5.07 mL, 2 equivalents), and the mixture wasstirred at 50° C. for 2 h. The solvent was evaporated and the residuewas purified using dichloromethane (100%)-25% ethylacetate/dichloromethane to give 2.97 g (63%) of the title compound.

Example 290D tert-butyl(2S)-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanoate

Example 290C (0.076 g, 0.297 mmol) was dissolved inN,N-dimethylformamide (1.5 mL) at 0° C. and treated with sodiumhexamethyldisilazide (0.33 mL, 1.1 equivalents, 1M in tetrahydrofuran)and the mixture is stirred for 1 h. The 4-chloromethyl-2-ethylthiazole(0.048 mg, 1 equivalent) was added (dissolved in 0.5 mLN,N-dimethylformamide) and the mixture was warmed to 25° C. for 2 h,heated to 75° C. for 18 h. The mixture was quenched with saturatedammonium chloride and partitioned between ethyl acetate and water, andthe organic was washed with brine and dried over MgSO₄, filtered andevaporated. The residue was purified using hexanes (100%)—65%hexanes/ethyl acetate to give 77 mg (68% yield) of the title compound.

Example 290E(2S)-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanoicacid

Example 290E (75 mg, 0.196 mmol) was dissolved in dichloromethane (1 mL)and trifluoracetic acid (1 mL), and the mixture was stirred at roomtemperature for 1 h. The solvent was evaporated and the crude productwas used directly for coupling procedures.

The compounds listed in Table 7, wherein X₁₁ and X₇ represents thepoints of connection to the core structure (E), were prepared by theprocedures as exemplified in Examples 289A-289E and Examples 290A-290E.

TABLE 7 (E)

Ex. R₁₁ R₇ 291

292

293

294

295

296

297

H 298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

357

358

359

360

Example 361(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanoicacid Example 361A tert-butyl(2S)-2-(3-{[2-(diethoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanoate

Example 290C (25 mg, 0.098 mmol) was dissolved in dichloromethane (1 mL)and treated with Example 273A (21.2 mg, 1 equivalent),triphenylphosphine (31 mg, 1.2 equivalents), anddiethyldiazodicarboxylate (18.2 pt, 1.2 equivalents), the mixture wasstirred at 25° C. for 1 h, quenched with water, the organic layer wasseparated, dried over magnesium sulfate, filtered, and the solvents wereevaporated. The crude residue was purified using dichloromethane(100%)—20% ethyl acetate/dichloromethane to give 28 mg (63%) of thetitle compound.

Example 361B tert-butyl(2S)-2-{3-[(2-formyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanoate

Example 361A (0.31 g, 0.68 mmol) was dissolved in acetone (14 mL) and 1MHCl (1.4 mL) and heated to 70° C. for 1 h. The solvents were evaporated,and the residue was partitioned between ethyl acetate and brine, theorganic layer was separated, washed with water, dried over magnesiumsulfate, and the solvents were evaporated to give crude 0.189 g (73%) ofthe title compound.

Example 361C tert-butyl(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanoate

Example 361B (0.12 g, 0.31 mmol) was dissolved in ethanol:benzene (1.2mL, 1:1) and treated with dimethylamine (0.79 mL, 2M in tetrahydrofuran)and heated to 70° C. for 2 h. The mixture was cooled to 25° C. andtreated with sodium cyanoborohydride (39.5 mg, 2 equivalents) and aceticacid (90 μL, 5 equivalents) and the reaction was quenched by saturatedammonium chloride after 1 h. The mixture was partitioned between waterand ethyl acetate, the organic layer was separated, washed with brine,dried over magnesium sulfate and the solvents were evaporated. The cruderesidue was purified using dichloromethane (100%)-4%methanol/dichloromethane to give 63 mg (49%) of the title compound.

Example 361D(2S)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylbutanoicacid

Example 361C (52 mg, 0.127 mmol) was dissolved in trifluoroaceticacid/dichloromethane (2 mL, 1:1) at 25° C. for 1 h. The solvents wereevaporated to give the crude acid trifluoroacetic acid salt.

Example 362(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide

Example 294 (47 mg) is combined with HOBT (28 mg, 1.5 equivalent) andEDAC (32 mg, 1.5 equivalents) in N,N-dimethylformamide (1 mL) andstirred for 1 h at 25° C. To this mixture is added N-methylmorpholine(NMM) (30 μL, 2 equivalents) and Example 18 (57 mg, 1 equivalent). Themixture is stirred for 16 h, evaporated under vacuum, and purified byHPLC (reverse phase; 95% water (0.1% trifluoroacetic acid)/5%acetonitrile to 100% acetonitrile; flow=10 mL/minute; time=30 minute) togive 51 mg (50%) of the title compound. ¹H NMR (300 MHz, CDCl₃) δ ppm0.79 (t, J=7.12 Hz, 6H), 0.86 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz,3H), 1.84 (m, 1H), 2.08 (m, 1H), 2.66 (dd, J=13.90, 10.85 Hz, 1H), 2.84(m, 1H), 3.12 (m, 5H), 3.47 (s, 3H), 3.60 (d, J=17.97 Hz, 1H), 3.85 (m,2H), 4.23 (m, J=4.41 Hz, 1H), 4.70 (s, 2H), 4.73 (d, J=14.58 Hz, 1H),4.81 (d, J=15.26 Hz, 1H), 6.39 (d, J=8.82 Hz, 1H), 7.07 (m, 5H), 7.24(s, 1H), 7.72 (d, J=8.14 Hz, 2H), 7.80 (d, J=8.48 Hz, 2H), 8.17 (s, 1H).

The compounds listed in Table 8, wherein X₇, X₁₁, and X₃ representrespectively the points of connection to the core structure (F), wereprepared by coupling the corresponding acids (Example 291-360) with thecorresponding amines (Example 1-31), using the procedure as exemplifiedby Example 362 (Method A) or Example 162 (Method B).

TABLE 8

Ex. Method R₁₁ R₇ R3 363 A

364 B

365 B

366 A

367 A

368 A

H

369 A

370 A

371 A

372 A

373 A

374 A

375 A

376 A

377 A

378 A

379 A

380 A

381 A

382 A

383 A

384 A

385 A

386 A

387 A

388 A

389 A

390 A

391 A

392 B

393 A

394 A

395 A

396 A

397 A

398 A

399 A

400 A

Example 401(2S)-2-[3-(3-aminobenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide

Example 363 (75 mg) was dissolved in ethyl acetate (1 mL) and combinedwith 10% Pd/C (30 mg), a hydrogen balloon, and stirred at 25° C. for 2h. The mixture was filtered, and the solvents were evaporated. Theresidue was purified using 2% methanol/CHCl₃ to give 45 mg (63%) of thetitle compound.

Example 402(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-(3-{3-[N-hydroxyethanimidoyl]benzyl}-2,4-dioxo-1-imidazolidinyl)-3-methylbutanamide

Example 376 (90 mg, 0.12 mmol) was dissolved in ethanol (2 mL) andtreated with hydroxylamine hydrochloride (34 mg, 4 equivalents) andtriethylamine (0.17 mL, 10 equivalents) at 50° C. for 3 h. The mixturewas cooled to 25° C. and partitioned between water and ethyl acetate.The organic layer was dried with sodium sulfate and the solvents wereevaporated. The crude residue was purified using 1% methanol/chloroformto give 55 mg (60%) of the title compound.

Example 403(2S)-2-{3-[3-(aminomethyl)benzyl]-2,4-dioxo-1-imidazolidinyl}-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylbutanamide

Example 382 (10 mg, 0.013 mmol) was dissolved in ethyl acetate (0.5 mL)and combined with Lindlar's catalyst (6 mg) and a hydrogen balloon andstirred for 2 h. The mixture was filtered, and the solvents wereevaporated. The residue was purified on florasil using 10%methanol/dichloromethane to give 5 mg (50%) of the title compound.

Example 404(2S,3S)-2-[3-(3-aminobenzyl)-2,4-dioxo-1-imidazolidinyl]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide

Example 390 (66 mg, 0.088 mmol) was dissolved in ethyl acetate (1 mL)and treated with 10% Pd/C (20 mg) and stirred at 25° C. under a hydrogenballoon for 3.5 h. The catalyst was filtered, and the solvents wereevaporated. The crude residue was purified using 2% methanol/chloroformto give 51 mg (80%) of the title compound.

Example 405(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-[3-({2-[N-hydroxyethanimidoyl]-4-pyridinyl}methyl)-2,4-dioxo-1-imidazolidinyl]-3-methylpentanamide

Example 381 (20 mg, 0.026 mmol) was dissolved in ethanol (0.3 mL) andtreated with hydroxylamine hydrochloride (7 mg, 4 equivalents) andtriethylamine (37 μL, 10 equivalents) at 50° C. for 6 h. The mixture wascooled to 25° C. and partitioned between water and ethyl acetate. Theorganic layer was dried with sodium sulfate and the solvents wereevaporated. The crude residue was purified using 5% methanol/chloroformto give 19 mg (100%) of the title compound.

Example 406methyl(2S,3S)-3-methyl-2-{[(4-nitrophenoxy)carbonyl]amino}pentanoate

To a solution of (L)-methyl iso-leucinate hydrochloride (2.5 g, 13.75mmol) in dichloromethane (35 mL) at 0° C. were added 4-nitrophenylchloroformate (3.05, 15.13 mmol) and N-methylmorpholine (3.2 mL, 29.11mmol), and the mixture was stirred at room temperature for 64 hours. Thereaction was partitioned between dichloromethane and saturated NaHCO₃,and the organic was washed with brine and dried over MgSO₄, filtered andevaporated to give the product (4.19 g, 98% yield), which was usedwithout further purification.

Example 407methyl(2S)-3-methyl-2-{[(4-nitrophenoxy)carbonyl]amino}butanoate

(L)-Methyl valinate (1 g) was dissolved in dichloromethane (10 mL) andtreated with bis-(4-nitrophenyl)carbonate (1.2 g, 1.1 equivalents) andN-methylmorpholine (1.5 mL, 2.5 equivalents) at 0° C. for 4 h. Thereaction was quenched with 1M NaHCO₃, and the organic layer wasseparated, washed with brine, dried with Na₂SO₄, filtered, andevaporated. The residue is purified using ethyl acetate/hexanes (2:3) togive 1.65 g (96%) of the title compound.

Example 408(2S)-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanoicacid Example 408A N-methyl(2-methyl-1,3-thiazol-4-yl)methanamine

2-Methyl-4-(chloromethyl)thiazole (2.94 g, CAS#39238-07-8) was dissolvedin 40% methylamine (39 mL, 25 equivalents) at 25° C. for 1 h. Themixture was evaporated and purified using 10% methanol/dichloromethanewith 0.5% NH₄OH to give 2.83 g (99%) of the amine.

Example 408Bmethyl(2S)-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanoate

Example 408A (2.83 g) was dissolved in tetrahydrofuran (80 mL) andtreated with triethyl amine (2.8 mL, 1 equivalent), DMAP (0.28 g, 0.02equivalent), and Example 407 (5.9 g, 1 equivalent) at 25° C. for 16 h.The mixture was quenched with 10% K₂CO₃, and the organic layer wasseparated, dried with Na2SO4, filtered, and evaporated to give the crudethiazole ester which was used directly in the next step.

Example 408C(2S)-3-methyl-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanoicacid

Example 408B (0.57 g) was dissolved in dioxane (8 mL) and treated with1.4M LiOH (8 mL, in water) at 25° C. for 1 h. The mixture was quenchedwith 1M HCl (4 mL), and the solvents were evaporated, and the residuewas purified using 5% methanol/dichloromethane to give 0.52 g (96%) ofthe acid.

The compounds listed in Table 9, wherein X₁₃ and X₇ represents thepoints of connection to the core structure (G), were prepared bycoupling of the p-nitrophenyl carbamates of the corresponding amino acidmethyl esters with the corresponding arylamines, heteroarylamines, andalkylamines by the procedures as exemplified in Example 406-408C.

TABLE 9 (G)

Ex. R₁₃ R₇ 409

410

411

412

413

414

415

416

417

418

419

420

421

422

423

424

425

426

427

428

429

430

431

432

433

Example 434(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-({[methyl(2-pyridinylmethyl)amino]carbonyl}amino)pentanamideMethod A

Example 421 (20 mg, 0.071 mmol) is combined with HOBT (9.6 mg, 1.5equivalent) and EDAC (14 mg, 1.5 equivalents) in N,N-dimethylformamide(1 mL) and stirred for 1 h at 25° C. To this mixture is addedN-methylmorpholine (NMM) (5.3 μL, 1 equivalent) and Example 18 (20 mg, 1equivalent). The mixture is stirred for 16 h, evaporated under vacuum,and purified by silica gel chromatography using 7%methanol/dichloromethane to give 13.4 mg (41%) of the title compound. ¹HNMR (300 MHz, CDCl₃) δ ppm 0.77 (m, 6H), 0.83 (d, J=6.78 Hz, 3H), 0.88(d, J=6.44 Hz, 3H), 0.97 (d, J=3.73 Hz, 1H), 1.88 (m, J=6.78 Hz, 2H),2.85 (m, 2H), 2.98 (m, 8H), 3.07 (m, 2H), 3.37 (dd, J=14.92, 4.75 Hz,1H), 3.85 (s, 1H), 4.14 (m, 1H), 4.22 (s, 2H), 4.31 (d, J=15.60 Hz, 1H),7.18 (m, 5H), 7.28 (s, 1H), 7.70 (d, J=8.48 Hz, 2H), 7.77 (s, 1H), 7.82(d, J=8.48 Hz, 2H), 8.12 (s, 1H), 8.20 (s, 1H).

Example 435(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[[(2-isopropyl-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylbutanamideMethod E

Example 409 (activated as O-succinimide ester) (75 mg, 0.18 mmol) wasdissolved in dichloromethane (1 mL) and N,N-dimethylformamide (0.5 mL)and treated with Example 18 (85 mg, 1.1 equivalents) andN-methylmorpholine (24.3 μL, 1.2 equivalents) at 25° C. for 16 h. Themixture was partitioned between dichloromethane and 1N NaHCO₃. Theorganic layer was separated, the solvents were evaporated, and theresidue was purified using 4% methanol/dichloromethane to give 70 mg(53%) of the title compound. ¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d,J=3.05 Hz, 3H), 0.78 (d, J=3.05 Hz, 3H), 0.84 (d, J=6.78 Hz, 3H), 0.89(d, J=6.78 Hz, 3H), 1.36 (d, J=6.44 Hz, 6H), 1.92 (m, 2H), 2.64 (dd,J=13.90, 10.51 Hz, 1H), 2.94 (s, 3H), 3.08 (m, 5H), 3.14 (m, 1H), 3.44(dd, J=14.92, 3.39 Hz, 1H), 3.79 (m, 1H), 3.95 (d, J=7.46 Hz, 1H), 4.06(m, 1H), 4.47 (t, J=16.28 Hz, 2H), 7.10 (m, 3H), 7.16 (s, 1H), 7.20 (m,2H), 7.76 (d, J=8.48 Hz, 2H), 7.82 (d, J=6.44 Hz, 2H), 8.13 (s, 1H).

The compounds listed in Table 10, wherein X₁₃, X₇ and X₃ representrespectively the points of connection to the core structure (H), wereprepared by coupling the corresponding acids (Example 409-433) with thecorresponding amines (Example 1-31) using the procedures as exemplifiedby Example 434 (Method A) or Example 435 (Method E).

TABLE 10

Ex. Method R₁₃ R₇ R₃ 436 A

437 A

438 A

439 A

440 E

441 E

442 A

443 A

444 A

445 A

446 A

447 A

448 A

449 A

450 A

451 A

452 A

453 A

454 A

455 A

456 A

457 A

458 A

459 A

460 A

461 A

462 A

463 A

464 A

465 A

Example 466(2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide

Example 444 (57 mg, 0.073 mmol) was treated with trifluoroaceticacid:dichloromethane (4 mL, 1:1) at 25° C. for 1 h. The solvents wereevaporated and the crude solid was triturated with ethyl acetate:hexanes1:5 to give 53 mg (99%) of the title compound.

Example 467(2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-({[{[2-(methoxymethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)butanamide

Example 445 (41 mg, 0.051 mmol) was dissolved indichloromethane:trifluoroacetic acid (4 mL, 1:1) at 25° C. for 1 h. Thesolvents were evaporated and the mixture was triturated with hexanes toprecipitate 38 mg (100%) of the title compound.

Example 468(2S,3S)-2-({[(3-aminobenzyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide

Example 453 (19 mg, 0.026 mmol) was dissolved in ethyl acetate (1 mL)and treated with 10% Pd/C (6 mg) at 25° C. for 3.5 h. The catalyst wasfiltered and the solvents were evaporated. The crude residue waspurified using 5% methanol/chloroform to give 17 mg (94%) of the titlecompound.

Example 469(2S,3R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide

Example 451 (25 mg) was dissolved in dichloromethane (2 mL) was treatedwith trifluoroacetic acid (2 mL) and stirred at 25° C. for 1 h. Thesolvents were evaporated. The residue was partitioned with saturatedNaHCO₃ and chloroform, and the organic layer was dried over Na₂SO₄ andevaporated to give 20 mg (98%) of the title compound.

Example 470(2S,3R)—N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-hydroxy-2-[({methyl[(2-methyl-1,3-thiazol-4-yl)methyl]amino}carbonyl)amino]butanamide

Example 452 was treated in a similar manner as in Example 469 to givethe title compound.

Example 471(2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamideExample 471A tert-butyl 2-amino-2-thioxoethylcarbamate

Boc-glycine (2.34 g, 0.134 mmol) was dissolved in dichloromethane (130mL) and treated with Lawesson's reagent (2.9 g, 0.52 equivalents) andthe mixture was stirred at 25° C. for 16 h. The mixture was filtered andthe solvents were evaporated. The residue was purified usingdichloromethane:ethyl acetate (1:1) to give 2.56 g (100%) of thethioamide.

Example 471Btert-butyl{4-[(methylamino)methyl]-1,3-thiazol-2-yl}methylcarbamate

Example 471A (0.5 g) was dissolved in isopropanol (10 mL) and treatedwith dichloroacetone (0.33 g, 1 equivalent) and the mixture was stirredat 25° C. for 16 h. The solvents were evaporated, and the crude residuewas dissolved in isopropanol (2 mL) and treated with 40% methylamine inwater (5 mL, 25 equivalents). The solvents were evaporated, and theresidue was partitioned between ethyl acetate and sat NaHCO₃. Theorganic layer was separated, dried over MgSO₄, filtered, and thesolvents were evaporated to give 0.48 g of the title compound.

Example 471Cmethyl(2S,3S)-2-({[[(2-{[(tert-butoxycarbonyl)amino]methyl}-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoate

Example 471B (0.48 g) was dissolved in tetrahydrofuran (10 mL) andtreated with triethyl amine (0.78 mL, 3 equivalent), DMAP (34 mg, 15 mol%) followed by Example 406 (0.7 g, 1.2 equivalent) and the mixture washeated to 66° C. for 16 h. The mixture was partitioned between ethylacetate and saturated NaHCO₃, the organic layer was separated, washedwith brine and dried over MgSO₄, filtered, and the solvents wereevaporated. The residue was purified using ethyl acetate to give 0.37 g(46%) of the title compound.

Example 471D(2S,3S)-2-({[[(2-{[(tert-butoxycarbonyl)amino]methyl}-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoicacid

Example 471C (0.37 g) was dissolved in tetrahydrofuran:water (4 mL, 3:1)and treated with LiOH (0.11 g, 3 equivalents) and the mixture wasstirred at 25° C. for 30 min. The mixture was quenched with 1N HCl (2.75mL) and partitioned between ethyl acetate and brine, the organic layerwas separated, dried over MgSO₄, filtered, and the solvents wereevaporated to give 0.36 g (100%) of the crude acid.

Example 471E tert-butyl(4-{(5S,8S,9R)-8-benzyl-9-hydroxy-11-({-4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)-2,13-dimethyl-5-[(1S)-1-methylpropyl]-3,6-dioxo-2,4,7,11-tetraazatetradec-1-yl}-1,3-thiazol-2-yl)methylcarbamate

Example 471D (35 mg) was dissolved in N,N-dimethylformamide (0.85 mL)and treated with EDAC (25 mg, 1.5 equivalents), HOBT (17 mg, 1.5equivalents), N-methylmorpholine (10 μL, 1.1 equivalents) followed byExample 18 (35 mg, 1 equivalent), and the mixture was stirred at 25° C.for 16 h. The solvents were evaporated and the residue was purified byHPLC reverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 74 mg (100%) ofthe title compound.

Example 471F tert-butyl(4-{(5S,8S,9R)-8-benzyl-9-hydroxy-11-({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)-2,13-dimethyl-5-[(1S)-1-methylpropyl]-3,6-dioxo-2,4,7,11-tetraazatetradec-1-yl}-1,3-thiazol-2-yl)methylcarbamate

Example 471E was dissolved in dichloromethane (2 mL) and trifluoroaceticacid (2 mL) and stirred at 25° C. for 30 min. The solvents wereevaporated, and the residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(95:5) to acetonitrile (100%) to give 61 mg (81%) of the title compound.

Example 472(2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclobutylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

Example 472 was prepared as for Example 471F using Example 471D andExample 19 followed by deprotection as in Example 471F to give the titlecompound.

Example 473(2S,3S)-2-({[{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

Example 473 was prepared as for Example 471F using Example 471D andExample 27 followed by deprotection as in Example 471F to give the titlecompound.

Example 474(2S,3S)-2-({[({2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamideExample 474A tert-butyl (1S)-2-amino-1-methyl-2-oxoethylcarbamate

To a solution containing Boc-L-alanine (1.0 g, 5.29 mmol) in a mixtureof tetrahydrofuran (25 mL) and N,N-dimethylformamide (5 mL) were addedEDAC (1.5 g, 7.82 mmol) and N-hydroxysuccinimide (0.91 g, 7.91 mmol) andthe mixture was stirred at room temperature for 16 hours. Aqueousammonium hydroxide solution (15 mL, 28%) was added and the mixture wasstirred for 0.5 hours at room temperature. The reaction was partitionedbetween ethyl acetate and water, and the organic was washed with brineand dried over MgSO₄, filtered and evaporated to give the product (0.483g, 49% yield), which was used without further purification.

Example 474B tert-butyl(1S)-2-amino-1-methyl-2-thioxoethylcarbamate

To Example 474A (0.48 g, 2.55 mmol) in dichloromethane (25 mL) was addedLawesons Reagent (0.54 g, 1.34 mmol), and the mixture was stirred atroom temperature for 16 hours. The solvent was evaporated and theresidue was purified using dichloromethane-35% ethyl acetate indichloromethane to give the product (0.52 g, 100% yield).

Example 474C ethyl2-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazole-4-carboxylate

To Example 474B (0.914 g, 4.48 mmol) in DME (7 mL) at −20° C. were addedpulverized KHCO₃ (3.55 g, 35.46 mmol) and ethyl bromopyruvate (1.65 mL,13.15 mmol), and the mixture was stirred at −20° C. for 1 hour. Asolution of trifluoroacetic anhydride (2.5 ml, 17.70 mmol) and2,6-lutidine (4.4 mL, 37.78 mmol) in dimethylether (4.5 mL) was added tothe reaction at −20° C. and the reaction was stirred at that temperaturefor 2 hours. The reaction was poured into water and was partitionedbetween ethyl acetate and water, and the organic was washed with brineand dried over MgSO₄, filtered and evaporated. The residue was purifiedusing dichloromethane-15% ethyl acetate in dichloromethane to give theproduct (1.26 g, 94% yield).

Example 474D tert-butyl(1S)-1-{4-[(methylamino)methyl]-1,3-thiazol-2-yl}ethylcarbamate

To Example 474C (0.50 g, 1.67 mmol) in a mixture of tetrahydrofuran (15mL) and methanol (1 mL) was added LiBH₄ (0.15 g, 6.89 mmol) and themixture was stirred at room temperature for 5 hours. The reaction waspartitioned between dichloromethane and water, and the organic waswashed with brine and dried over MgSO₄, filtered and evaporated. To asolution of this product (1.67 mmol) were added triethylamine (0.70 mL,5.02 mmol) and methanesulfonyl chloride (0.195 mL, 2.52 mmol) at 0° C.and the reaction was stirred at this temperature for 0.5 hours. Thereaction was partitioned between dichloromethane and water, and theorganic was washed with brine and dried over MgSO₄, filtered andevaporated to give the crude mesylate. To an aqueous solution ofmethylamine (5 mL, 40%) was added a solution of the mesylate (1.67 mmol)in 2-propanol (2 mL) and the mixture was stirred at room temperature for1.5 hours. The solvent was removed under reduced pressure to give theproduct (0.305 g), which was used without further purification.

Example 474Fmethyl(2S,3S)-2-({[[(2-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoate

Example 474D (0.305 g, 1.13 mmol) was dissolved in tetrahydrofuran (6mL) and treated with Example 406 (0.525 g, 1.69 mmol), triethylamine(0.47 mL, 3.37 mmol), and DMAP (0.020 g, 0.16 mmol), at room temperatureand the mixture was stirred at 80° C. for 16 hours. The reaction wascooled and partitioned between ethyl acetate and saturated NaHCO₃, andthe organic was washed with brine and dried over MgSO₄, filtered andevaporated. The residue was purified using dichloromethane-ethyl acetateto give the product (0.344 g, 69% yield).

Example 474G(2S,3S)-2-({[[(2-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoicacid

To Example 474F (0.344 g, 0.778 mmol) in dioxane (3 mL) was added anaqueous solution of lithium hydroxide (3.0 mL, 0.5 M), and the reactionwas stirred for 0.5 hours at room temperature. Aqueous HCl (1.62 mL, 1N) was added and the reaction was partitioned between ethyl acetate andwater, and the organic was washed with brine and dried over MgSO₄,filtered and evaporated to give the product, which was used withoutfurther purification.

Example 474H tert-butyl(1S)-1-(4-{(5S,8S,9R)-8-benzyl-12-cyclopentyl-9-hydroxy-11-({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)-2-methyl-5-[(1S)-1-methylpropyl]-3,6-dioxo-2,4,7,11-tetraazadodec-1-yl}-1,3-thiazol-2-yl)ethylcarbamate

Example 474G (35 mg) was dissolved in N,N-dimethylformamide (0.85 mL)and treated with EDAC (25 mg, 1.5 equivalents), HOBT (17 mg, 1.5equivalents), N-methylmorpholine (10 μL, 1.1 equivalents) followed byExample 27 (35 mg, 1 equivalent), and the mixture was stirred at 25° C.for 16 h. The solvents were evaporated and the residue was purified byHPLC reverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 74 mg (100%) ofthe title compound.

Example 474I(2S,3S)-2-({[({2-[(1S)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

Example 474H was dissolved in dichloromethane (2 mL) and trifluoroaceticacid (2 mL) and stirred at 25° C. for 30 min. The solvents wereevaporated, and the residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(95:5) to acetonitrile (100%) to give 61 mg (81%) of the title compound.

Example 475(2S,3S)-2-({[({2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

In a similar manner to Example 474 but starting with Boc-(D)-alanine,Example 475 was prepared via coupling and deprotection.

Example 476(2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[({6-[N-hydroxyethanimidoyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-3-methylpentanamideExample 476A 1-[6-(hydroxymethyl)-2-pyridinyl]ethanone

The title compound was prepared according to the procedure as describedin Katsura, Y. et. al., Journal of Medicinal Chemistry, 37, 57-66(1994).

Example 476B 1-[6-(chloromethyl)-2-pyridinyl]ethanone

To Example 476A (0.23 g, 1.52 mmol) in N,N-dimethylformamide (2 mL) at0° C. was treated phosphorus oxychloride (0.283 mL, 3.04 mmol). Themixture was stirred 3 hours at 0° C., quenched with 1M sodiumbicarbonate, and extracted with ethyl acetate. The organic layer wasevaporated, and the residued was purified using 10% ethyl acetate/hexaneto give 86 mg (33.4%) of the title compound.

Example 476C 1-{6-[(methylamino)methyl]-2-pyridinyl}ethanone

Example 476B (86 mg, 0.5 mmol) at 25° C. was treated with 2 Mmethylamine in tetrahydrofuran (2 mL, 4 mmol). The reaction was stirredat 25° C. for 16 hour, the solvent was concentrated and the residue waspurified using 10% methanol/dichloromethane with 0.5% ammonium hydroxideto give 53 mg (72.6%) of the title compound.

Example 476D tert-butyl(2S,3S)-2-({[[(6-acetyl-2-pyridinyl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoate

To Example 476C (50 mg, 0.3 mmol), Example 406 (107 mg, 0.3 mmol) inN,N-dimethylformamide (2 mL) at 25° C. was treated withdiisopropylethylamine (64 μL, 0.36 mmol) followed byN,N-dimethylaminopyridine (5.2 mg, 0.042 mmol). The mixture was stirredfor 16 hour, quenched with 1M sodium bicarbonate, and extracted withethyl acetate. The organic layer was evaporated, and the residued waspurified using 30% ethyl acetate/hexane to give 97 mg (84.4%) of thetitle compound.

Example 476E(2S,3S)-2-({[[(6-acetyl-2-pyridinyl)methyl](methyl)amino]carbonyl}amino)-3-methylpentanoicacid

Example 476D (97 mg, 0.257 mmol) at 25° C. was treated with 80%trifluoroacetic acid in dichloromethane (1.5 mL). The reaction wasstirred at 25° C. for 3 hour, the solvent was concentrated and theresidue was dissolved in water (0.5 mL) and purified using 7%methanol/dichloromethane to give 100 mg (89.3%) of the title compound.

Example 476F(2S,3S)-2-({[[(6-acetyl-2-pyridinyl)methyl](methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

Example 476E (99 mg, 0.31 mmol) was dissolved in N,N-dimethylformamide(3 mL) and combined with EDAC (88 mg, 1.5 equivalents), HOBT (62 mg, 1.5equivalents), and N methylmorpholine (34 μL, 1 equivalent) followed byaddition of Example 27 (164 mg, 1.2 equivalents). The mixture wasstirred for 4 d at 25° C., quenched with 1N NaHCO₃, and extracted withethyl acetate. The solvents were evaporated and the residue was purifiedusing 5% methanol/dichloromethane to give 84 mg (47%) of the ketone.

Example 476G(2S,3S)—N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-2-({[({6-[N-hydroxyethanimidoyl]-2-pyridinyl}methyl)(methyl)amino]carbonyl}amino)-3-methylpentanamide

Example 476F (75 mg) was dissolved in methanol (2 mL) and combined withhydroxylamine hydrochloride (14 mg, 2 equivalents). The mixture wasstirred at 25° C. for 16 h. The solvents were evaporated and the residuewas purified using 10% methanol/dichloromethane to give 54 mg (70%) ofthe title compound.

Example 477(2S,3S)-2-({[({2-[(1S)-1-(acetylamino)ethyl]-1,3-thiazol-4-yl}methyl)(methyl)amino]carbonyl}amino)-N-{(1S,2R)-1-benzyl-3-[(cyclopentylmethyl)({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-2-hydroxypropyl}-3-methylpentanamide

Example 474I (0.87 g) was dissolved in dichloromethane (0.2 mL) andtreated with triethyl amine (3.2 μL, 2 equivalents) and acetic anhydride(1.3 μL, 1.2 equivalents), and the mixture was stirred at 25° C. for 3h. The solvents were evaporated, and the residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 11.3 mg (100%)of the title compound.

Example 478 tert-butyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropylcarbamateMethod D

(L)-Boc-t-leucine (55 mg, 0.024 mmol) was dissolved in tetrahydrofuran(10 mL) and treated with triethyl amine (66 μL, 2 equivalents),3-(diethylphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) (86 mg,1.2 equivalents), and Example 18 (0.1 g, 1 equivalent) at 25° C. for 16h. The mixture was partitioned between ethyl acetate and 10% Na₂CO₃, theorganic layer was separated, washed with water, brine, dried overNa₂S_(Q), and the solvents were evaporated. The residue was purifiedusing ethyl acetate:hexanes (1:2) to give 0.114 g (76%) of the titlecompound. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (m, 15H), 1.42 (s, 9H),1.85 (m, 1H), 2.84 (m, 1H), 2.95 (m, 1H), 3.02 (m, 1H), 3.13 (m, 1H),3.69 (d, J=8.46 Hz, 1H), 3.85 (m, 2H), 4.12 (q, J=7.11 Hz, 1H), 4.19 (m,1H), 4.94 (s, 1H), 6.00 (d, J=8.46 Hz, 1H), 7.22 (m, 5H), 7.70 (d,J=8.82 Hz, 2H), 7.76 (d, J=8.46 Hz, 2H), 8.16 (s, 1H).

Example 479hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamateExample 479A hexahydrofuro[2,3-b]furan-3-yl 4-nitrophenyl carbonate

To a solution of (3S,3aR,6aS)- and(3R,3aS,6aR)-3-hydroxy-4H-hexahydrofuro[2,3-b]furan (see compound 15 in:Gosh, A. K.; Kincaid, J. F.; Walters, D. E.; Chen, Y.; Chaudhuri, N. C.;Thompson, W. J.; Culberson, C.; Fitzgerald, P. M. D.; Lee. H. Y.; McKee,S. P.; Munson, P. M.; Duong, T. T.; Darke, P. L.; Zugay, J. A.; Schleif,W. A.; Axel, M. G.; Lin, J.; Huff, J. R. Journal of Medicinal Chemistry1996, 39, 3278-3290.) (1.5 g, 11.5 mmol) in dichloromethane (40 mL) at0° C. were added N-methylmorpholine (1.9 mL, 17.3 mmol) and4-nitrophenyl chloroformate (2.9 g, 14.4 mmol), and the mixture wasstirred for 16 hours at 0° C. The solvent was evaporated under reducedpressure and the residue was chromatographed on silica gel, eluting with25% ethyl acetate in hexanes to give the product (291 g, 86% yield).

Example 479Bhexahydrofuro[2,3-b]furan-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propylcarbamateMethod F

Example 479A (10.6 mg, 0.036 mmoles, 1.5 equivalents) was combined withExample 18 (10 mg, 0.024 mmoles) in tetrahydrofuran (0.5 mL) at 25° C.for 24 h. The solvent was evaporated under vacuum, and the residue waspurified using 2% methanol/dichloromethane to give 10.9 mg (80% yield)of the title compound. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (dd, J=6.44,3.73 Hz, 3H), 0.93 (m, 3H), 1.84 (s, 2H), 2.85 (m, 2H), 3.01 (m, 3H),3.16 (m, 1H), 3.59 (dd, J=9.66, 6.61 Hz, 1H), 3.69 (m, 1H), 3.85 (m,3H), 3.96 (m, 2H), 4.93 (dd, J=16.95, 8.14 Hz, 1H), 5.01 (s, 1H), 5.66(m, 1H), 7.27 (m, 5H), 7.55 (d, J=2.03 Hz, 1H), 7.72 (d, J=8.48 Hz, 2H),7.78 (m, 2H), 8.16 (s, 1H).

The compounds listed in Table 11, wherein X₃ and X₅ representrespectively the points of connection to the core structure (I), wereprepared by coupling available activated acids and carbonates withExamples 1-31 as exemplified in Example 434 (Method A) or Example 162(Method 131, Example 435 (Method E), or Example 479 (Method F).

TABLE 11 I

Ex. Method R₅ R₃ 480 F

481 A

482 A

483 B —X₅

484 A

485 A

486 A

487 A

488 A

489 F

490 F

491 A

492 E

493 E

494 E

495 A

496 F

497 F

498 A

499 E

500 A

501 A

502 A

503 A

504 E

505 A

506 A

507 A

508 A

509 A

510 F

511 F

512 F

Example 513(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamideExample 513A methyl(2S)-2-[(chloroacetyl)amino]-3,3-dimethylbutanoate

(L)-methyl t-leucinate hydrochloride (1 g) was dissolved in ethylacetate (6 mL) and water (4 mL) and treated with K₂CO₃ (1.66 g, 3equivalents) followed by chloroacetyl chloride (0.53 mL, 1.2equivalents) at 25° C. for 2 h. The organic layer was separated, washedwith 10% citric acid, and the solvents were evaporated. The residue waspurified by ethyl acetate:hexanes (1:4) to give 1.22 g (100%) of thechloro ester.

Example 513Bmethyl(2S)-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanoate

Example 513A (1.22 g) was dissolved in tetrahydrofuran (5 mL) andtreated with 3-fluorobenzyl amine (1.9 mL, 3 equivalents) at 60° C. for16 h. The solvents were evaporated and the residue partitioned between1N NaHCO₃ and ethyl acetate. The organic layer was separated andpurified using ethyl acetate:hexanes (3:2) to give 1.22 g (71%) of thetitle compound.

Example 513Cmethyl(2S)-2-({[(tert-butoxycarbonyl)(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanoate

Example 513B (1.22 g) was dissolved in dioxane (14 mL) and treated with1N NaHCO₃ (9 mL, 2.3 equivalents) followed by Boc₂O (1.11 g, 1.3equivalents) at 25° C. for 16 h. The mixture was partitioned betweenwater and ethyl acetate, the organic layer separated, and the solventswere evaporated. The residue was purified using ethyl acetate:hexanes(1:4) to give 1.55 g (96%) of the protected amine.

Example 513D2-({[(tert-butoxycarbonyl)(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanoicacid

Example 513C (1 g) was dissolved in tetrahydrofuran (6 mL) and treatedwith LiOH (0.133 g, 1.3 equivalents) in water (3 mL) at 0° C. for 16 h.The solvents were evaporated, and the residue was partitioned betweenwater and ethyl acetate. The aqueous layer was separated, acidified with10% citric acid to pH 2-3, and extracted with ethyl acetate. The organiclayer was separated, and the solvents were evaporated. The residue waspurified using 10% methanol/dichloromethane to give 0.9 g (93%) of theacid as epimers at the alpha center which were not separable.

Example 513E tert-butyl2-({(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropyl}amino)-2-oxoethyl(3-fluorobenzyl)carbamate

Example 513D (0.125 g) was dissolved in N,N-dimethylformamide (2 mL) andtreated with EDAC (82 mg, 1.5 equivalents), HOBT (58 mg, 1.5equivalents), followed by Example 18 (0.12 g, 0.9 equivalent) at 25° C.for 3 d. The mixture was partitioned between 1N NaHCO₃ and ethylacetate. The organic layer was separated, and the solvents wereevaporated. The residue was separated using ethyl acetate:hexanes (1:1)to give 0.21 g of Example 514E and 0.36 g of Example 513E.

Example 513F(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide

Example 513E (0.105 g) was dissolved in 80% trifluoroacetic acid (3 mL)at 25° C. for 2 h. The solvents were evaporated, and the residue waspurified using 10% methanol/ethyl acetate w/0.5% NH₄OH to give 53 mg(58%) of the title compound.

Example 514(2R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamideExample 514E tert-butyl2-({(1R)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2,2-dimethylpropyl}amino)-2-oxoethyl(3-fluorobenzyl)carbamateExample 514F(2R)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3,3-dimethylbutanamide

Example 514E (0.11 g) was deprotected as for Example 513F to give 74 mg(81%) of the title compound.

Example 515(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3-methylpentanamideExample 515A

N-Boc-glycyl-(L)-isoleucine (0.5 g) was dissolved in tetrahydrofuran (25mL) and treated with Boc₂O (0.64 g, 1.1 equivalents) and 1N NaOH (2.66mL, 1 equivalent) at 25° C. for 2 h. The mixture was partitioned betweenNaHCO₃ and dichloromethane. The aqueous layer was separated, acidifiedwith 10% citric acid, and extracted with dichloromethane. The organiclayer was separated, dried with MgSO4, filtered, and the solvents wereevaporated to give 0.3 g (39%) of the Boc compound.

Example 515B tert-butyl2-({(1S,2S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-2-methylbutyl}amino)-2-oxoethylcarbamate

Example 515A (34 mg) was dissolved in N,N-dimethylformamide (3 mL) andtreated with EDAC (25 mg, 1.1 eq), HOBT (18 mg, 1.1 equivalents), andExample 18 (50 mg, 1 equivalent) at 25° C. for 16 h. The mixture waspartitioned dichloromethane and 1N NaHCO₃, the organic layer wasseparated, dried over MgSO₄, and the solvents were evaporated. Theresidue was purified using ethyl acetate:hexanes (2:1) to give 67 mg(82%) of the amide.

Example 515C(2S,3S)-2-[(aminoacetyl)amino]-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methylpentanamide

Example 515B (0.44 g) was dissolved in dichloromethane (2 mL) andtrifluoroacetic acid (8 mL) at 25° C. for 2.5 h. The solvents wereevaporated, and the residue was dissolved in dichloromethane, washedwith 0.5N NH₄OH, dried with MgSO4, filtered, and the solvents wereevaporated to give 0.378 g (100%) of the title compound.

Example 515D(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-2-({[(3-fluorobenzyl)amino]acetyl}amino)-3-methylpentanamide

Example 515C (12 mg) was dissolved in methanol (1 mL) and benzene (1 mL)and treated with 3-fluorobenzaldehyde (2.2 μL, 1 equivalent), and thismixture is heated to 50° C. for 1.5 h. The mixture is cooled and treatedwith NaBH₄ (3.8 mg, 5 equivalents) at 25° C. for 1 h. The mixture wasquenched with water and dichloromethane, the organic layer wasseparated, dried with MgSO4, filtered, and the solvents were evaporated.The residue was purified using ethyl acetate with 1% NH₄OH to give 4.7mg (33%) of the title compound.

Example 517(2S,3S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-[({[(5-nitro-3-thienyl)methyl]amino}acetyl)amino]pentanamide

In a similar manner to Example 515D, the title compound was prepared bycoupling 2-nitrothiophene-3-carboxaldehyde with Example 515C.

Example 518benzyl(1S)-4-{[amino(imino)methyl]amino}-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamateExample 518Abenzyl(1S)-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]-4-[((Z)-[(tert-butoxycarbonyl)amino]{[(Z)-tert-butoxycarbonyl]imino}methyl)amino]butylcarbamate

Z-Arginine(Boc)₂OH cyclohexylamine salt (22 mg) was dissolved in water,acidified with 10% citric acid and extracted with ethyl acetate. Theorganic layer was separated, dried over Na₂SO₄, and the solvents wereevaporated to give the free acid. This acid was dissolved inN,N-dimethylformamide (0.5 mL) and treated with EDAC (13.7 mg, 1.5equivalents), HOBT (9.66 mg, 1.5 equivalents), and N-methylmorpholine(5.3 μL, 1 equivalent) followed by the Example 18 (20 mg, 1 equivalent)at 25° C. for 2 d. The mixture was partitioned between 1N NaHCO₃ andethyl acetate. The organic layer was separated, and the solvents wereevaporated. The residue was purified using 5% ethyl acetate/hexanes togive 21 mg (48%) of the di-Boc compound.

Example 518Bbenzyl(1S)-4-{[amino(imino)methyl]amino}-1-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)carbonyl]butylcarbamate

Example 518A (21 mg) was dissolved in 80% trifluoroacetic acid (1 mL) at25° C. for 2 h. The solvents were evaporated and purified by preparativeTLC using 0.25 mm plates and 8% methanol/dichloromethane/1% NH₄OH togive 9 mg (55%) of the title compound.

Example 519(2S)-2-amino-N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}-3,3-dimethylbutanamide

Example 478 was treated with trifluoroacetic acid as for Example 518B togive the title compound.

Example 520N-{(2R,3S)-2-hydroxy-3-[({4-(hydroxyimino)methyl]phenyl}sulfonyl)amino]-4-phenylbutyl}-4-[(E)-(hydroxyimino)methyl]-N-isobutylbenzenesulfonamideExample 520A(acetyloxy){4-[({(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]propyl}amino)sulfonyl]phenyl}methylacetate

Example 18 (78.6 mg) was dissolved in tetrahydrofuran (1 mL) andN,N-dimethylformamide (0.1 mL) and treated with the product of Example17 from Part 1 of Method B, (70.5 mg, 1.2 equivalents) and triethylamine (78 μL, 3 equivalents) at 25° C. for 2 h. The solvents wereevaporated, and the residue was purified using dichloromethane to give87 mg (68%) of the sulfonamide.

Example 520BN-{(2R,3S)-2-hydroxy-3-[({4-[(hydroxyimino)methyl]phenyl}sulfonyl)amino]-4-phenylbutyl}-4-[(E)-(hydroxyimino)methyl]-N-isobutylbenzenesulfonamide

Example 520A (87 mg) was dissolved in ethanol (1.2 mL) and treated withhydroxylamine hydrochloride (19 mg, 1.5 equivalents) and triethyl amine(91 μL, 3.5 equivalents) at 75° C. for 1 h. The solvents wereevaporated, and the residue was purified using dichloromethane to give88 mg (100%) of the title compound.

Example 521N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamideExample 521Atert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propylcarbamate

To a solution of(2R,3S)-3-N-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (0.2 g,0.76 mmol) in 2-propanol (4 mL) was added the isobutylamine (1.5 mL, 20equivalents), and the mixture was heated at 80° C. for 2 hours. Thesolvents were evaporated, and the crude residue was dissolved indichloromethane (8 mL) and treated with triethylamine (0.32 mL, 3equivalents) and p-methoxybenzenesulfonyl chloride (0.173 g, 1.1equivalents) and the mixture is stirred at 25° C. for 1 h. The solventswere evaporated and the crude residue was purified using 0.5%methanol/dichloromethane to give 0.356 g (92%) of the title compound.

Example 521BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-methoxybenzenesulfonamide

Example 521A (47 mg, 0.093 mmol) was dissolved in trifluoroaceticacid:dichloromethane (4 mL, 1:1) at 25° C. for 1 h. The solvents wereevaporated to give 38 mg (100%) of the title compound.

The compounds listed in Table 12, wherein X₃ represents respectively thepoints of connection to the core structure (J), were prepared by theprocedures as exemplified in Example 521A and Example 521B, substitutingcyclopentylmethylamine and neopentylamine, respectively, forisobutylamine

TABLE 12 J

Ex. R₃ 522

523

Example 524(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[(2-isopropyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamideMethod C

Example 144 (25 mg) was combined with N-hydroxysuccinimide (10 mg, 1.1equivalents) and DCC (18 mg, 1.1 equivalents) in dichloromethane (1 mL)and stirred for 1 h at 25° C. The solids are filtered, and to thismixture was added N-methylmorpholine (9 μL, 1 equivalent) and Example521B (31 mg, 1 equivalent). The mixture was stirred for 16 h,evaporated, and was purified using 1% methanol/chloroform to give 33 mg(60%) of the title compound. ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (dd,J=10.51, 6.44 Hz, 3H), 0.81 (dd, J=6.61, 2.88 Hz, 3H), 1.30 (d, J=2.37Hz, 3H), 1.32 (d, J=2.37 Hz, 3H), 1.94 (m, 1H), 2.40 (dd, J=13.73, 11.02Hz, 1H), 3.04 (m, 6H), 3.28 (s, 3H), 3.40 (m, 1H), 3.61 (s, 1H), 3.75(d, J=10.85 Hz, 1H), 3.83 (s, 3H), 3.87 (s, 1H), 4.02 (s, 2H), 4.30 (d,J=15.60 Hz, 1H), 4.39 (d, J=13.22 Hz, 1H), 4.43 (d, J=7.80 Hz, 1H), 4.93(d, J=6.44 Hz, 1H), 5.56 (d, J=7.80 Hz, 2H), 7.07 (m, 7H), 7.24 (s, 1H),7.71 (d, J=8.82 Hz, 2H), 7.86 (d, J=9.49 Hz, 1H).

The compounds listed in Table 13, wherein X₉, X₇, and X₃ representrespectively the points of connection to the core structure (J), wereprepared by coupling the corresponding acids (Examples 32-160) with thecorresponding amines (Examples 521-523) as exemplified in Example 362(Method A) or Example 161 (Method B), Example 524 (Method C) and Example478 (Method D).

TABLE 13

Ex. Method R₉ R₇ R₃ 525 A

526 C

527 C

528 C

529 A

530 A

531 A

532 A

533 A

534 A

535 A

536 A

537 A

538 A

539 C

540 A

541 A

542 A

543 A

544 A

545 A

546 A

547 A

548 A

549 A

550 A

551 A

552 A

553 A

554 A

555 A

556 A

557 A

558 B

559 B

560 B

561 B

562 B

563 B

564 A

565 B

566 A

567 B

568 B

569 A

570 A

571 B

572 B

573 B

574 A

575 A

576 A

577 A

578 A

579 D

580 D

581 D

582 A

583 B

584 B

585 A

586 D

Example 587(2S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamideExample 587A tert-butyl(2S)-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanoate

Example 273D (509 mg) was dissolved in ethanol (14 mL) added NaBH₄ (57.6mg, 1.1 equivalents). The mixture was stirred at 25° C. for 3 h andquenched with sat. NH₄Cl and the mixture was partitioned between ethylacetate and water. The organic layer was separated, washed with brine,dried over MgSO₄. The solvents were evaporated to give 452 mg (88%)crude alcohol.

Example 587B tert-butyl(2S)-3-methyl-2-{3-[(2-{[(methylsulfonyl)oxy]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoate

Example 587A (452 mg) was dissolved in dichloromethane (12 mL) addedtriethylamine (683 μL, 4 equivalents), cooled to 0° C. andmethanesulfonyl chloride (190 μL, 2 equivalents). After 30 min. thesolvents were evaporated. The residue was partitioned between ethylacetate and 10% citric acid solution. The organic layer was separatedand washed with 10% NaHCO₃, brine, dried over MgSO₄, filtered, and thesolvents were evaporated to give 335 mg (61%) of the title compound.

Example 587C(2S)-2-(3-{[2-(azidomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanoicacid

Example 587B (335 mg) was dissolved in N,N-dimethylformamide (5 mL) andLiN₃ (366 mg, 10 equivalents) and the mixture was heated to 50° C. for2.5 h. The solvents were evaporated and partitioned between ethylacetate and brine, and the organic layer was separated, dried overMgSO₄, filtered, and concentrated to give 292 mg of crude azide. Thecrude azide was dissolved in dichloromethane (2 mL) and trifluoroaceticacid (2 mL) and stirred at 25° C. for 2 h. The solvents were evaporatedto give 244 mg (96%) acid.

Example 587D(2S)-2-(3-{[2-(azidomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide

Example 587C (244 mg) was dissolved in N,N-dimethylformamide (7 mL) andHOBT (146 mg, 1.5 equivalents), EDAC (168 mg, 1.5 equivalents),triethylamine (0.2 mL, 2 equivalents) followed by Example 521B (352 mg,1.2 equivalents). The mixture was stirred at 25° C. for 16 h. Thesolvents were evaporated, and the residue was purified usingdichloromethan:ethyl acetate (100:0 to 0:100) to give 333 mg (64%) ofthe azide.

Example 587E(2S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide

Example 587D (270 mg, 0.37 mmol) was dissolved in tetrahydrofuran (3 mL)and water (0.7 mL) followed by triphenylphosphine (TPP) (195 mg, 2equivalents). The mixture was heated to 50° C. for 1 h. The mixture waspartitioned between dichloromethane and water. The organic layer wasseparated, washed with brine, dried over MgSO₄ and the solvents wereevaporated. The residue was purified using dichloromethane:ethyl acetate(1:1 to 100:0 to 10% methanol/dichloromethane) to give 215 mg (83%) ofthe title compound.

Example 588

(2S)-2-[3-({2-[(acetylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylbutanamide

Example 587E (11 mg, 0.016 mmol) was dissolved in dichloromethane (0.15mL) and treated with acetic anhydride (2.2 μL, 1.5 equivalents) andtriethylamine (6.6 μL, 3 equivalents) at 25° C. for 1 h. The mixture wasquenched with citric acid and washed with 10% NaHCO₃, brine, dried overMgSO₄, filtered, and the solvents were evaporated. The residue waspurified using dichloromethane:methanol (100:0 to 95:5) to give 9.8 mg(84%) of the title compound.

Example 589(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide

Example 550 (45 mg, 0.062 mmol) was dissolved in tetrahydrofuran:water(1 mL, 2:1) and treated with LiOH (8 mg) at 25° C. for 30 min. Themixture is quenched with 1N HCl (0.2 mL) and partitioned between ethylacetate and water, the organic layer is separated, washed with brine anddried over MgSO₄, filtered, and the solvents were evaporated to give 43mg (100%) of the title compound.

Example 590(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide

Example 587E (50 mg, 0.071 mmol) was dissolved in acetonitrile (0.7 mL)added formaldehyde (27 μL, 5 equivalents) acetic acid (8.1 μL, 2equivalents), NaCNBH₃ (9 mg, 2 equivalents). The mixture was stirred at25° C. for 3 h. The solvents were evaporated and the residue waspurified using dichloromethane:methanol (95:5) to give 9 mg (17%) of thetitle compound.

Example 591

(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-{[(methylsulfonyl)amino]methyl}-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 587E (16.5 mg, 0.023 mmol) was dissolved in dichloromethane(0.25 mL) and treated with mesyl chloride (2 μL, 1.1 equivalents) andtriethylamine (9.8 μL, 3 equivalents) at 0° C. for 1 h. The solventswere evaporated and the residue was purified using 5%methanol/dichloromethane to give 12 mg (66%) of the title compound.

Example 592(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(hydroxyimino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide

Example 587E (10.2 mg, 0.0145 mmol) was dissolved in dichloromethane(0.2 mL) at 0° C. was treated with m-chloroperbenzoic acid (7 mg, 2equivalents) and the mixture was stirred for 2 h. The mixture wasquenched with 50% NaHCO₃ and extracted with ethyl acetate. The organiclayer was separated and dried over MgSO₄, filtered, and the solventswere evaporated. The residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(95:5) to acetonitrile (100%) to give 7 mg (45%) of the title compound.

Example 593methyl(4-{[3-((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2-oxo-1-imidazolidinyl]methyl}-1,3-thiazol-2-yl)methylcarbamate

Example 587E (16.7 mg, 0.023 mmol) was dissolved in dichloromethane (0.4mL) was treated with triethylamine (6.6 μL, 2 equivalents) and methylchloroformate (2 μL, 1.1 equivalents) at 0° C. for 30 min. The solventswere evaporated and the residue was purified by HPLC reverse phasechromatography using water (0.1% trifluoroacetic acid):acetonitrile(95:5) to acetonitrile (100%) to give 12 mg (67%) of the title compound.

Example 594(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylsulfonyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamideExample 594Atert-butyl(2S)-3-methyl-2-[3-({2-[(methylsulfanyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanoate

Example 587B (28 mg, 0.062 mmol) was dissolved in N,N-dimethylformamide(0.6 mL) and treated with sodium methylthiolate (4.8 mg, 1.1equivalents) at 25° C. for 16 h. The mixture was partitioned betweensaturated NH₄Cl and ethyl acetate. The organic layer was separated anddried over MgSO₄, filtered, and the solvents were evaporated. Theresidue was purified using ethyl acetate:dichloromethane (1:1) to give17.4 mg (70%) of the title compound.

Example 594B(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylsulfanyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide

Example 594A (57 mg, 0.142 mmol) was dissolved in dichloromethane (1 mL)and trifluoroacetic acid (1 mL) and stirred at 25° C. for 1 h. Thesolvents were evaporated and the crude acid used directly for the nextstep. The acid was dissolved in N,N-dimethylformamide (1 mL) and treatedwith EDAC (33 mg, 1.5 equivalents), HOBT (29 mg, 1.5 equivalents), Nmethylmorpholine (0.16 mL, 1 equivalent) followed by the Example 18 (58mg, 1 equivalent) and the mixture was stirred at 25° C. for 16 h. Thesolvents were evaporated and the residue was purified usingdichloromethane:ethyl acetate (1:1) to give 12 mg (11%) of the titlecompound.

Example 594C(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylsulfonyl)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide

Example 594B (13 mg, 0.017 mmol) was dissolved in dichloromethane (0.4mL) and treated with m-chloroperbenzoic acid (8.7 mg, 2 equivalents) at25° C. for 30 min. The solvents were evaporated and the residue waspurified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give11.2 mg (82%) of the title compound.

Example 595(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[(diethylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide

Example 587E was treated in a similar manner as for Example 590 usingacetaldehyde instead of formaldehyde was to prepare the title compound.

Example 596(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isopropylamino)-2-oxoethyl]-2-oxo-1-imidazolidinyl}-3-methylbutanamide

Example 620B (5.8 mg, 0.008 mmol) was dissolved in ethanol (0.3 mL) andtreated with NaBH₄ (5 mg) and the mixture was stirred at 25° C. for 16h. The solvents were evaporated and the residue was directly used forthe next step. The imidazolone was dissolved in HOAc (1 mL) and treatedwith Pd(OH)₂ and a hydrogen balloon. The mixture was stirred for 16 h,filtered, and the solvents were evaporated. The residue was purified byHPLC reverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 2.7 mg (46%from imide) of the title compound.

Example 597(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamideExample 597A tert-butyl(2S)-3-methyl-2-[3-({2-[(methylamino)methyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanoate

Example 273D (200 mg, 0.54 mmol) was dissolved in toluene:ethanol (2.2mL, 1:1) was added 2M methylamine in tetrahydrofuran (0.54 mL, 2equivalents) was heated to 70° C. for 2 h. The mixture was cooled to 25°C. and NaBH₄ (20 mg, 3 equivalents) was added and the mixture wasstirred at 25° C. for 16 h. The solvents were evaporated and the residuewas partitioned between ethyl acetate and sat. NaHCO₃, the organic layerwas separated and washed with brine, dried over MgSO₄, filtered, andevaporated. The residue was purified using chloroform:methanol (95:5) togive 118 mg (56%) of the title compound.

Example 597B tert-butyl(2S)-2-{3-[(2-[[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino]methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}-3-methylbutanoate

Example 597A (118 mg, 0.3 mmol) was dissolved in dichloromethane (3 mL)a 0° C. and triethylamine (90 μL, 2.2 equivalents) followed by FMOC-Cl(86 mg, 1.1 equivalents). The mixture was stirred at 25° C. for 16 h.The solvents were evaporated and the residue was purified using ethylacetate:hexanes (1:1) to give 138 mg (76%) of protected amine.

Example 597C9H-fluoren-9-ylmethyl(4-{[3-((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2-oxo-1-imidazolidinyl]methyl}-1,3-thiazol-2-yl)methyl(methyl)carbamate

Example 597B (60 mg, 0.099 mmol) was dissolved in dichloromethane (0.5mL) and trifluoroacetic acid (0.5 mL) and stirred at 25° C. for 1 h. Thesolvents were evaporated and the acid was used directly for the nextstep. The crude acid was dissolved in N,N-dimethylformamide (1 mL) withHOBT (20 mg, 1.5 equivalents) EDAC (29 mg, 1.5 equivalents), andN-methylmorpholine (27 μL, 2.5 equivalents) followed by the Example 18(40 mg, 1 equivalent). The mixture was stirred at 25° C. for 16 h andthe solvents were evaporated. The residue was purified using HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 40 mg (42%) ofthe title compound.

Example 597D(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-[3-({2-[(methylamino)methy1]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]butanamide

Example 597C (40 mg, 0.042 mmol) was dissolved in acetonitrile (0.5 mL)and diethylamine (10 μL, 3 equivalents), and the mixture was stirred at25° C. for 1 h. The solvents were evaporated and the residue waspurified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give13 mg (37%) of the title compound.

Example 598(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-[3-({2-[N-hydroxyethanimidoyl]-1,3-thiazol-4-yl}methyl)-2-oxo-1-imidazolidinyl]-3-methylbutanamide

Example 540 was treated in a similar manner to Example 476G to give thetitle compound.

Example 599(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-3-methylpentanamideExample 599A9H-fluoren-9-ylmethyl(4-{[3-((1S,2S)-1-{[((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)amino]carbonyl}-2-methylbutyl)-2-oxo-1-imidazolidinyl]methyl}-1,3-thiazol-2-yl)methylcarbamate

Example 279F (15 mg, 0.027 mmol) was dissolved in N,N-dimethylformamide(0.3 mL) and treated with Example 522 (18 mg, 1.5 equivalents), EDAC (8mg, 1.5 equivalents), HOBT (6 mg, 1.5 equivalents), andN-methylmorpholine (7 μL, 2.5 equivalents) at 25° C. for 16 h. Thesolvents were evaporated, and the residue was purified by HPLC reversephase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (75:25) to acetonitrile (100%) to give 12 mg (46%) ofthe title compound.

Example 599B(2S,3S)-2-(3-{[2-(aminomethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-3-{(cyclopentylmethyl)[(4-methoxyphenyl)sulfonyl]amino}-2-hydroxypropyl)-3-methylpentanamide

Example 599A (12 mg, 0.012 mmol) was dissolved in acetonitrile (0.2 mL)and treated with diethylamine (3 μL, 3 equivalents) at 25° C. for 2 h.The solvents were evaporated, and the residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 10.6 mg (100%)of the title compound.

Example 600(2S,3S)-2-(3-{3-[amino(hydroxyimino)methyl]benzyl}-2-oxo-1-imidazolidinyl)-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methylpentanamide

Example 570 (80 mg, 0.11 mmol) was dissolved in ethanol (1 mL) andtreated with hydroxylamine hydrochloride (32 mg, 4 equivalents) andtriethylamine (0.16 mL, 10 equivalents) at 50° C. for 9 h. The mixturewas partitioned between water and ethyl acetate, the organic layer wasseparated, dried over Na₂SO₄, and the solvents were evaporated. Theresidue was purified using ethyl acetate to give 35 mg (42%) of thetitle compound.

Example 601(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-4-hydroxy-2-{3-[(1-methyl-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExample 601Abenzyl(1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-3-hydroxypropylcarbamate

Example 521B (167 mg, 0.41 mmol) was dissolved in pyridine (0.4 mL) andtreated with Z-aminobutyrolactone (193 mg, 2 equivalents)(CAS#35677-89-5) and heated to 100° C. for 2 d. The solvents wereevaporated and the residue was purified using ethyl acetate to give 235mg (66%) of the title compound.

Example 601B(2S)-2-amino-N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-4-hydroxybutanamide

Example 601A (73 mg, 0.11 mmol) was dissolved in methanol (2 mL) andtreated with Pd(OH)₂/C and stirred with a hydrogen balloon at 25° C. for3 h. The mixture was filtered, rinsed with methanol, and the solventswere evaporated. The amine was used directly without purification.

Example 601C 9H-fluoren-9-ylmethyl2-[((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-3-hydroxypropyl)amino]ethyl[(1-methyl-1H-benzimidazol-2-yl)methyl]carbamate

Example 601B (58 mg, 0.11 mmol) and Example 148C (49 mg, 1 equivalent)were dissolved in methanol (0.5 mL) and HOAc (5 μL) and treated withNaCNBH₃ (15.4 mg, 2 equivalents) at 25° C. for 2 h. The mixture waspartitioned between water and ethyl acetate, the organic layer wasseparated and washed with 10% NaHCO₃, brine and the solvents wereevaporated. The residue was purified using 9% methanol/dichloromethaneto give 81 mg (78%) of the title compound.

Example 601D(2S)—N—((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-4-hydroxy-2-{3-[(1-methy1-1H-benzimidazol-2-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 601C (81 mg, 0.088 mmol) was dissolved in N,N-dimethylformamide(0.9 mL) and treated with diethylamine (90 μL) at 25° C. for 1 h. Thesolvents were evaporated and the residue was dissolved in dichloroethane(1.8 mL) and treated with bis(p-nitrophenyl) carbonate (34 mg, 1.1equivalents) and heated to 50° C. for 16 h. The mixture was partitionedwith ethyl acetate and 1N Na₂CO₃ and stirred for 1 h, and the organiclayer was separated. This layer was washed several times with 1N Na₂CO₃,separated, and the solvents were evaporated. The residue was purifiedusing 9% methanol/dichloromethane to give 46 mg (72%) the titlecompound.

Example 602(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamideMethod C

Example 292 (50 mg) was combined with N-hydroxysuccinimide (28 mg, 1.1equivalents) and DCC (49 mg, 1.1 equivalents) in dichloromethane (1 mL)and stirred for 1 h at 25° C. The solids are filtered, and to thismixture was added N-methylmorpholine (35 μL, 1 equivalent) and Example521B (72 mg, 1 equivalent). The mixture was stirred for 16 h,evaporated, and was purified using 1% methanol/chloroform to give 74 mg(65%) of the title compound. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd,J=8.99, 6.61 Hz, 6H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (m, 3H), 1.82 (m,1H), 2.08 (m, 1H), 2.30 (m, 1H), 2.78 (m, 2H), 3.01 (m, 2H), 3.07 (m,2H), 3.23 (m, 1H), 3.58 (d, J=17.97 Hz, 1H), 3.81 (m, 3H), 3.88 (s, 3H),3.94 (m, 1H), 4.23 (m, 1H), 4.73 (d, J=6.10 Hz, 2H), 4.81 (s, 1H), 4.86(d, J=10.17 Hz, 1H), 6.21 (d, J=9.49 Hz, 1H), 6.99 (m, 2H), 7.11 (m,6H), 7.72 (m, 2H), 8.02 (s, 1H).

The compounds listed in Table 14, wherein X₁₁, X₇, and X₃ representrespectively the points of connection to the core structure (E), wereprepared by coupling the corresponding acids (Examples 291-360) with thecorresponding amines (Examples 521-523) as exemplified in Example 362(Method A) or Example 162 (Method B) or Example 602 (Method C).

TABLE 14

Ex. Cpd # R₁₁ R₇ R₃ 603 C

604 A

605 B

606 B

607 A

608 A

609 B

610 B

611 B

612 B

613 A

614 A

615 B

616 A

617 A

618 A

619 A

Example 620(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isopropylamino)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamideExample 620A[3-((1S)-1-{[((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)amino]carbonyl}-2-methylpropyl)-2,5-dioxo-1-imidazolidinyl]aceticacid

Example 607 (161 mg, 0.24 mmol) was dissolved in tetrahydrofuran:water(0.9 mL, 3:1) and treated with LiOH (11 mg, 1.1 equivalents) at 25° C.for 2 h. The mixture was quenched with trifluoroacetic acid (20 μL), thesolvents were evaporated and the residue was purified using 10% methanol(2% HOAc)/ethyl acetate to give 0.125 g (81%) of the acid.

Example 620B(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propyl)-2-{3-[2-(isopropylamino)-2-oxoethyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide

Example 620A (24 mg, 0.037 mmol) was dissolved in N,N-dimethylformamide(0.4 mL) and treated with EDAC (10 mg, 1.5 equivalents), HOBT (7.5 mg,1.5 equivalents), followed by isopropylamine (5 μL, 1 equivalent) andthe mixture was stirred at 25° C. for 16 h. The solvents wereevaporated, and the residue was purified using acetonitrile to give 12mg (47%) of the title compound.

The compounds listed in Table 15, wherein X₀ represents the point ofconnection to the core structure (L), were prepared using the proceduresas exemplified in Example 620A and Example 620B.

TABLE 15 L

Ex# R₀ 621

622

623

624

Example 625N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutylbenzenesulfonamideExample 625AN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-(benzyloxy)-N-isobutylbenzenesulfonamide

Example 1 (0.13 g, 0.39 mmol) was dissolved in dichloromethane (4 mL)and treated with triethylamine (0.12 mL, 2.2 equivalents) andp-benzyloxybenzenesulfonyl chloride (0.12 g, 1.1 equivalents) at 25° C.for 18 h. The crude mixture was purified using chloroform to give 0.22 g(97%) of the title compound.

Example 625BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutylbenzenesulfonamide

Example 625A (0.22 g, 0.38 mmol) was dissolved in ethyl acetate (4 mL)and treated with Pd(OH)₂/C (0.1 g) and a hydrogen balloon at 25° C. for2 h. The crude mixture was filtered, and the solvents were evaporated togive 0.2 g crude solid. This material was dissolved indichloromethane:trifluoroacetic acid (6 mL, 1:1) at 25° C. for 1 h. Thesolvents was evaporated, the crude residue was azeotroped twice withtoluene to give 0.205 g (100%) crude amine as the trifluoroacetic acidsalt.

Example 6264-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutylbenzenesulfonamideExample 626Atert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-nitrophenyl)sulfonyl]amino}propylcarbamate

Example 1 (0.64 g, 1.9 mmol) was dissolved in dichloromethane (20 mL)and treated with triethylamine (0.8 mL, 3 equivalents) andp-nitrobenzenesulfonyl chloride (0.46 g, 1.1 equivalents) at 25° C. andstirred for 4 h. The reaction mixture was evaporated and purified using7% ethyl acetate/dichloromethane to give 0.88 g (89%) of the titlecompound.

Example 626B 4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutylbenzenesulfonamide

Example 626A (0.88 g, 1.7 mmol) was dissolved in ethyl acetate (17 mL)and treated with 20% Pd(OH)₂/C (230 mg, 0.2 equivalent) and a hydrogenballoon at 25° C. for 1 h. The crude mixture was filtered and thesolvents were removed by evaporation. This material was dissolved indichloromethane:trifluoroacetic acid (10 mL, 1:1) at 25° C. for 1 h. Thesolvents were evaporated, the crude residue was azeotroped twice withethyl acetate to give 0.75 g (100%) of crude product as thetrifluoroacetic acid salt.

Example 6273-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-chloro-N-isobutylbenzenesulfonamideExample 627Atert-butyl(1S,2R)-1-benzyl-3-[[(4-chloro-3-nitrophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropylcarbamate

Example 1 (0.64 g, 1.9 mmol) was dissolved in dichloromethane (20 mL)and treated with triethylamine (0.8 mL, 3 equivalents) andp-chloro-o-nitrobenzenesulfonyl chloride (0.54 g, 1.1 equivalent) at 25°C. and stirred for 4 h. The reaction mixture was evaporated and purifiedusing 5% ethyl acetate/dichloromethane to give 0.88 g (85%) of the titlecompound.

Example 627B3-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-chloro-N-isobutylbenzenesulfonamide

Example 627A (0.85 g, 1.53 mmol) was dissolved in ethanol:acetic acid(20 mL 1:1) and treated with iron (330 mg, 4 equivalents). The reactionwas heated to 70° C. for 1 h. The reaction was evaporated and extractedtwice with ethyl acetate. The organic layer was washed twice withsaturated NaHCO₃, dried over MgSO₄, filtered, and evaporated to give0.91 g of crude product. This material was treated withdichloromethane:trifluoroacetic acid (20 mL, 1:1) at 25° C. for 1 h. Thesolvents were evaporated to yield 0.80 g of Example 627B (100%).

Example 6283-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutylbenzenesulfonamideExample 628A 4-(benzyloxy)-3-nitrobenzenesulfonyl chloride

To 10 g (41.5 mmol) of 4-hydroxy-3-nitro-benzenesulfonic acid sodiumsalt dissolved in ethanol (250 mL) was added benzyl bromide (5.4 mL, 1.1equivalents), 15% NaOH solution (13.2 mL, 1.2 equivalents), and water(40 mL). The mixture was heated to 70° C. for 5 h. Additional benzylbromide (5.4 mL) and 15% NaOH solution (13 mL) was added and heating wascontinued for an additional 18 h. The ethanol was removed byevaporation. The reaction was filtered through a pad of Celite, washedwith water, and dried in a vacuum oven at 50° C. to give 7 g ofmaterial. A portion of this material (1.5 g, 4.56 mmol) was combinedwith phosphorous pentachloride (1.14 g, 1.2 equivalents) and phosphorousoxychloride (1.4 mL, 3.3 equivalents) and heated to 100° C. for 18 h.The reaction mixture was partitioned between chloroform and water. Theorganic layer was washed with a brine solution, dried over MgSO₄,filtered, and evaporated to leave 1.4 g of crude title compound whichwas used in the subsequent step.

Example 6288tert-butyl(1S,2R)-1-benzyl-3-[{[4-(benzyloxy)-3-nitrophenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropylcarbamate

Example 1 (1.5 g, 4.4 mmol) was dissolved in 25 mL of dichloromethaneand treated with Example 628A (1.4 g, 4.2 mmol) and triethylamine (1.3mL, 2.2 equivalents). The reaction was stirred at 25° C. for 3 h. Thecrude mixture was purified using chloroform to give 1.83 mg (74%) of thetitle compound.

Example 628C3-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutylbenzenesulfonamide

Example 628B (450 mg, 0.72 mmol) was dissolved in ethyl acetate (60 mL)and treated with 20% Pd(OH)₂/C (200 mg, 0.1 equivalent) and a hydrogenfilled balloon at 25° C. for 3 h. The reaction was filtered andevaporated to leave 376 mg of crude material. This was dissolved indichloromethane:trifluoroacetic acid (6 mL, 1:1) and stirred at 25° C.for 1.5 h. The solvents were removed by evaporation and the product wasazeotroped with toluene (3×). The material was dissolved in ethylacetate, washed with saturated NaHCO₃ solution, washed with brine, driedover MgSO₄, filtered, and evaporated to leave 328 mg (100%) of the titlecompound.

Example 629N-(5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenyl)-1-methy1-1H-imidazole-4-sulfonamide Example 629A(1R,2S)-1-{[{[4-(benzyloxy)-3-nitrophenyl]sulfonyl}(isobutyl)amino]methyl}-2-[(tert-butoxycarbonyl)amino]-3-phenylpropylacetate

Example 628B (1.83 g, 2.9 mmol) was dissolved in dichloromethane (30 mL)and treated with triethylamine (0.6 mL, 1.5 equivalents), aceticanhydride (0.3 mmol, 1.1 equivalents), and a catalytic amount of4-(dimethylamino)pyridine. The reaction was stirred at 25° C. for 18 hand purifie using ethyl acetate/hexane to yield 1.82 g (93%) of thetitle compound.

Example 629B(1R,2S)-1-{[{[3-amino-4-(benzyloxy)phenyl]sulfonyl}(isobutyl)amino]methyl}-2-[(tert-butoxycarbonyl)amino]-3-phenylpropylacetate

Example 629A (1.8 g, 2.7 mmol) was dissolved ethanol (25 mL) and aceticacid (5 mL). The solution was treated with iron powder (600 mg, 4equivalents) and heated to 50° C. for 1.5 h. The solvents were removedby evaporation. The reaction was dissolved in chloroform and washed witha saturated solution of NaHCO₃, washed with brine, dried over MgSO₁,filtered and evaporated. The residue was purified using chloroform andethyl acetate to give 651 mg (38%) of the title compound.

Example 629C(1R,2S)-1-{[[(4-(benzyloxy)-3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}phenyl)sulfonyl](isobutyl)amino]methyl}-2-[(tert-butoxycarbonyl)amino]-3-phenylpropylacetate

Example 629B (75 mg, 0.12 mmol) was dissolved in 1 mL of dichloromethaneand treated with triethylamine (0.049 mL, 3 equivalents),1-methylimidazole-4-sulfonyl chloride (32 mg, 1.5 equivalents), and acatalytic amount of 4-(dimethylamino)pyridine. The reaction was stirredat 40° C. for 4 h. The reaction was purified using 2% methanol/CHCl₃ togive 36 mg (39%) of the title compound.

Example 629Dtert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}phenyl)sulfonyl](isobutyl)amino]propylcarbamate

Example 629C (24 mg, 0.031 mmol) was dissolved in 1 mL of methanol andtreated with 20% Pd(OH)₂/C (20 mg) and stirred at 25° C. under ahydrogen balloon atmosphere for 1 h. The reaction was filtered andevaporated to give 19 mg of crude product. This material (19 mg, 0.027mmol) was dissolved in 0.5 mL of methanol and treated with KO₃ (4.2 mg,1.1 equivalents) and stirred at 25° C. for 3 h. The reaction wasevaporated and purified using 7% methanol/CHCl₃ to give 5.1 mg of thetitle compound (26%).

Example 629EN-(5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenyl)-1-methyl-1H-imidazole-4-sulfonamide

Example 629D (5 mg, 0.008 mmol) was dissolved indichloromethane:trifluoroacetic acid (0.5 mL, 2:1) and stirred at 25° C.for 1 h. The reaction was evaporated and azeotroped with toluene (3×) togive the title compound.

Example 630N-(5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenyl)-3-pyridinesulfonamideExample 630A 3-pyridinesulfonyl chloride

A mixture of 3-pyridinesulfonic acid (1.0 g, 6.3 mmol), phosphorouspentachloride (1.6 g, 1.2 mmol), and phosphorous oxychloride (2.0 mL,3.3 mmol) was combined and stirred at 100° C. for 18 h. The reaction wascooled to 25° C., diluted with CHCl₃, and bubbled with HCl gas. Theresulting precipitate was collected by filtration, washed with CHCl₃,and dried in vacuo to yield 1.12 g of the title compound (84%).

Example 630B(1R,2S)-1-{[({4-(benzyloxy)-3-[(3-pyridinylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]methyl}-2-[(tert-butoxycarbonyl)amino]-3-phenylpropylacetate

Example 629B (75 mg, 0.12 mmol) was dissolved in 1.2 mL ofdichloromethane and treated with pyridine (0.033 mL, 3.5 equivalents)and Example 630A (43 mg, 1.7 equivalents) at 25° C. and stirred for 72h. The reaction was evaporated and purified using 25% ethylacetate/chloroform to yield 67 mg of the title compound (72%).

Example 630Ctert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-hydroxy-3-[(3-pyridinylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate

Example 630B (67 mg, 0.086 mmol) was dissolved in 1 mL of methanol andtreated with K₂CO₃ (15 mg, 1.2 equivalents) at 25° C. for 18 h. Thereaction was diluted with chloroform and washed with a saturatedsolution of NH₄Cl, which was back extracted with chloroform. Theorganics were combined and washed with brine, dried over MgSO₄,filtered, and evaporated to yield 66 mg of crude product. This materialwas dissolved in 1 mL of methanol and treated with 20% Pd(OH)₂/C (30 mg,0.5 mmol) and stirred at 25° C. under hydrogen balloon pressure for 2 h.The reaction was filtered, evaporated, and purified using 5%methanol/CHCl₃ to give 22.8 mg (40%) of the title compound.

Example 630DN-(5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenyl)-3-pyridinesulfonamide

Example 630C (22 mg, 0.034 mmol) was dissolved indichloromethane:trifluoroacetic acid (0.4 mL, 1:1) and stirred at 25° C.for 1.5 h. The reaction was evaporated and azeotroped with toluene (3×)to give the title compound.

Example 631N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-[(methylsulfonyl)amino]benzenesulfonamideExample 631A(1R,2S)-1-{[({4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]methyl}-2-[(tert-butoxycarbonyl)amino]-3-phenylpropylacetate

Example 628B (75 mg, 0.11 mmol) was dissolved in 1.1 mL ofdichloromethane, cooled to −78° C. and treated with pyridine (0.027 mL,3 equivalents), and methanesulfonyl chloride (0.016 mL, 1.8equivalents). The reaction was allowed to warm to 25° C. and stirred for18 h. The reaction mixture was evaporated and purified using 20% ethylacetate/chloroform to give 91 mg of the title compound (99%).

Example 631Btert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[({4-hydroxy-3-[(methylsulfonyl)amino]phenyl}sulfonyl)(isobutyl)amino]propylcarbamate

Example 631A (90 mg, 0.13 mmol) was dissolved in 1.3 mL of methanol,treated with K₂CO₃ (21 mg, 1.2 equivalents), and stirred at 25° C. for1.5 h. The reaction was diluted with chloroform and washed with asaturated solution of NH₄Cl, which was back extracted with CHCl₃. Theorganics were combined and washed with brine, dried over MgSO₄,filtered, and evaporated to yield 83 mg of crude product. This materialwas dissolved in 1.2 mL of methanol and treated with 20% Pd(OH)₂/C (40mg) and stirred at 25° C. under hydrogen balloon pressure for 2 h. Thereaction was filtered, evaporated, and purified using 5% methanol/CHCl₃to give 38 mg (52%) of the title compound.

Example 631CN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-[(methylsulfonyl)amino]benzenesulfonamide

Example 631B (35 mg, 0.060 mmol) was dissolved indichloromethane:trifluoroacetic acid (0.3 mL, 1:1) and stirred at 25° C.for 1.5 h. The reaction was evaporated and azeotroped with toluene (3×)to give the title compound.

Example 632N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3,5-dichloro-4-hydroxy-N-isobutylbenzenesulfonamide

3,5-dichloro-4-hydroxy benzenesulphonyl chloride (97 mg, 0.372 mmol) wasdissolved in 1 mL of dichloromethane and treated withN,O-bis(trimethylsilyl)acetamide (0.092 mL, 1 equivalent) and stirred at25° C. for 5 h. The reaction mixture was treated with Example 1 (100 mg,0.8 equivalents) and triethylamine (0.109 mL, 2.1 equivalents) andstirred an additional hour. The reaction was diluted withdichloromethane washed with water, dried over MgSO₄, filtered, andevaporated to give 240 mg of a foamy solid. This material was stirredwith dichloromethane:trifluoroacetic acid (4.5 mL, 2:1) for 1.5 h. Thereaction was evaporated, redissolved in 10% methanol/dichloromethane,washed with saturated NaHCO₃ solution, and purified using 10%methanol/dichloromethane to give 80 mg of the title compound (58%).

Example 633N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3,5-dichloro-2-hydroxy-N-isobutylbenzenesulfonamide

3,5-dichloro-6-hydroxy benzenesulphonyl chloride (97 mg, 0.372 mmol) wasdissolved in 1 mL of dichloromethane and treated withN,O-bis(trimethylsilyl)acetamide (0.092 mL, 1 equivalent) and stirred at25° C. for 5 h. The reaction mixture was treated with Example 1 (100 mg,0.8 equivalents) and triethylamine (0.109 mL, 2.1 equivalents) andstirred an additional hour. The reaction was diluted withdichloromethane washed with water, dried over MgSO₄, and evaporated togive 240 mg of a foamy solid. This material was stirred withdichloromethane:trifluoroacetic acid (4.5 mL, 2:1) for 1.5 h. Thereaction was evaporated, redissolved in 10% methanol/dichloromethane,washed with saturated NaHCO₃ solution, and purified using 10%methanol/dichloromethane to give 79 mg of the title compound (57%).

Example 634N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-methylbenzenesulfonamideExample 634A 4-(benzyloxy)-3-methylbenzenesulfonyl chloride

O-Cresol-4-sulfonic acid (6 g, 31.88 mmol) was stirred with benzylbromide (9.5 mL, 2.5 equivalent), 15% aqueous NaOH (34 mL, 4equivalents), and ethanol (150 mL) at 67° C. for 22 h. The solvent wasevaporated and the reaction was slurried with 10 mL of water, filtered,and the resulting white solid was washed with water twice. The materialwas dried in vacuo to give 8.2 g of the O-benzylated sodium salt. Aportion of this material (4.0 g, 15.1 mmol) was stirred with phosphorouspentachloride (4.4 g, 1.5 equivalents) for 10 minutes. The mixture waspartitioned between dichloromethane and water. The organic layer wasseparated, dried over MgSO₄, filtered and the solvent was removed byevaporation to give 3.29 g (77%) of the title compound.

Example 634Btert-butyl(1S,2R)-1-benzyl-3-[{[4-(benzyloxy)-3-methylphenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropylcarbamate

Example 1 (100 mg, 0.30 mmol) dissolved in 2 mL of dichloromethane wascombined with Example 634A (1 mg, 1.2 equivalents) and triethylamine(0.0125 mL, 3 equivalents) and stirred for 4 h. The reaction waspurified using 1% methanol/dichloromethane to give 200 mg (100%) ofcrude title compound.

Example 634CN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-methylbenzenesulfonamide

Example 634B (200 mg crude, 0.3 mmol) was dissolved in 2 mL of ethanoland treated with 10% Pd/C (100 mg). The reaction was stirred underhydrogen balloon pressure for 24 h. The reaction was filtered,evaporated, and purified using 1% methanol/dichloromethane to give 80 mgof the debenzylated product. This material was stirred withdichloromethane:trifluoroacetic acid (3 mL, 2:1) for 2.5 h. The solventswere evaporated, and the product was dissolved in dichloromethane,washed with NaHCO₃, dried over MgSO₄, filtered and concentrated to yield70 mg (57%) of the title compound.

Example 635N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-5-fluoro-4-hydroxy-N-isobutyl-2-methylbenzenesulfonamideExample 635A 5-fluoro-4-hydroxy-2-methylbenzenesulfonyl chloride

To a solution of chlorosulfonic acid (1.5 g, 13.3 mmol) dissolved in 10mL of dichloromethane was added 2-fluoro-5-methylphenol (1.1 g, 8.86mmol) dropwise. After 10 minutes, the reaction was quenched by adding toice water. The reaction was extracted with dichloromethane, washed withbrine, dried over MgSO₄, filtered, and concentrated to give 150 mg(7.5%) of the title compound.

Example 635BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-5-fluoro-4-hydroxy-N-isobutyl-2-methylbenzenesulfonamide

Example 635A (95 mg, 0.424 mmol) was dissolved in 1 mL ofdichloromethane, treated with N,O-bis(trimethylsilyl)acetamide (0.105mL, 1 equivalent), and stirred at 25° C. for 5 h. The reaction mixturewas treated with Example 1 (100 mg, 0.7 equivalent), triethylamine(0.109 mL, 2.1 equivalents), and stirred an additional hour. Thereaction was diluted with dichloromethane washed with water, dried overMgSO₄, filtered, and evaporated give a foamy solid. This material wasstirred with dichloromethane:trifluoroacetic acid (4.5 mL, 2:1) for 1.5h. The reaction was evaporated, redissolved in 10%methanol/dichloromethane, washed with saturated NaHCO₃ solution, andpurified using 10% methanol/dichloromethane to give 53 mg of the titlecompound (42%).

Example 636N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-5-chloro-4-hydroxy-N-isobutyl-2-methylbenzenesulfonamideExample 636A 5-chloro-4-hydroxy-2-methylbenzenesulfonyl chloride

To a solution of chlorosulfonic acid (1.22 g, 10.5 mmol) dissolved in 10mL of dichloromethane was added 2-chloro-5-methylphenol (1.0 g, 7.0mmol) dropwise. After 10 minutes, the reaction was quenched by pouringit into ice water. The reaction was extracted with dichloromethane,washed with brine, dried over MgSO₄, filtered, and concentrated to give120 mg (7.1%) of the title compound.

Example 636BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-5-chloro-4-hydroxy-N-isobutyl-2-methylbenzenesulfonamide

Example 636A (120 mg, 0.50 mmol) was dissolved in 1 mL ofdichloromethane, treated with N,O-bis(trimethylsilyl)acetamide (0.123mL, 1 equivalent), and stirred at 25° C. for 5 h. The reaction mixturewas treated with Example 1 (117 mg, 0.7 equivalent), triethylamine(0.106 mL, 2.1 equivalents), and stirred an additional hour. Thereaction was diluted with dichloromethane, washed with water, dried overMgSO₄, filtered, and evaporated to give a foamy solid. This material wasstirred with dichloromethane:trifluoroacetic acid (4.5 mL, 2:1) for 1.5h. The reaction was evaporated, redissolved in 10%methanol/dichloromethane, washed with saturated NaHCO₃ solution, andpurified using 10% methanol/dichloromethane to give 33 mg (21%) of thetitle compound.

Example 637N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-chloro-4-hydroxy-N-isobutyl-5-methylbenzenesulfonamideExample 637A 3-chloro-4-hydroxy-5-methylbenzenesulfonyl chloride

To a solution of chlorosulfonic acid (1.22 g, 10.5 mmol) dissolved in 10mL of dichloromethane was added 2-chloro-5-methylphenol (1.0 g, 7.0mmol) dropwise. After 10 minutes, the reaction was quenched by pouringit into ice water. The reaction was extracted with dichloromethane,washed with brine, dried over MgSO₄, filtered, and concentrated to give190 mg (11.3%) of the title compound.

Example 637BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-chloro-4-hydroxy-N-isobutyl-5-methylbenzenesulfonamide

Example 637A (190 mg, 0.788 mmol) was dissolved in 2 mL ofdichloromethane, treated with N,O-bis(trimethylsilyl)acetamide (0.194mL, 1 equivalent), and stirred at 25° C. for 5 h. The reaction mixturewas treated with Example 1 (183 mg, 0.7 equivalent), triethylamine(0.230 mL, 2.1 equivalents), and stirred an additional hour. Thereaction was diluted with dichloromethane, washed with water, dried overMgSO₄, and evaporated to give a foamy solid. This material was stirredwith dichloromethane:trifluoroacetic acid (4.5 mL, 2:1) for 2 h. Thereaction was evaporated, redissolved in 10% methanol/dichloromethane,washed with saturated NaHCO₃ solution, and purified using 7%methanol/dichloromethane to give 110 mg (46%) of the title compound.

Example 638N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-chloro-4-hydroxy-N-isobutyl-5-methylbenzenesulfonamideExample 638A 2-chloro-4-hydroxy-5-methylbenzenesulfonyl chloride

To a solution of chlorosulfonic acid (3.69 g, 31.65 mmol) dissolved in30 mL of dichloromethane was added 3-chloro-6-methylphenol (3.0 g, 21.1mmol) dropwise. After 10 minutes, the reaction was quenched by pouringit into ice water. The reaction was extracted with dichloromethane,washed with brine, dried over MgSO₄, filtered, and concentrated to give120 mg (2.4%) of the title compound.

Example 638BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-2-chloro-4-hydroxy-N-isobutyl-5-methylbenzenesulfonamide

Example 638A (120 mg, 0.497 mmol) was dissolved in 2 mL ofdichloromethane, treated with N,O-bis(trimethylsilyl)acetamide (0.135mL, 1.1 equivalents), and stirred at 25° C. for 5 h. The reactionmixture was treated with Example 1 (132 mg, 0.7 equivalent),triethylamine (0.164 mL, 2.1 equivalents), and stirred an additionalhour. The reaction was diluted with dichloromethane, washed with water,dried over MgSO₄, filtered, and evaporated to give a foamy solid. Thismaterial was stirred with dichloromethane:trifluoroacetic acid (4.5 mL,2:1) for 2 h. The reaction was evaporated, redissolved in 10%methanol/dichloromethane, washed with saturated NaHCO₃ solution, andpurified using 7% methanol/dichloromethane to give 25 mg (14.5%) of thetitle compound.

Example 639N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-{[(methylamino)sulfonyl]amino}benzenesulfonamideExample 639A 4-hydroxy-3-nitrobenzenesulfonyl chloride

To a solution of chlorosulfonic acid (12.0 mL, 180 mmol) at 0° C. wasadded 2-nitrophenol (8.35 g, 60.0 mmol) in small portions over 1 h. Thereaction was heated to 60° C. for 20 minutes and allowed to stir for 18h at 25 C. The reaction was quenched by pouring it into 100 g of ice.The reaction was extracted with chloroform (3×), washed with cold water(2×), dried over MgSO₄, filtered, and concentrated to give 9.06 g (64%)of the title compound.

Example 639Btert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-nitrophenyl)sulfonyl](isobutyl)amino]propylcarbamate

Example 639A (1.06 g, 4.46 mmol) was dissolved in 22 mL ofdichloromethane, treated with N,O-bis(trimethylsilyl)acetamide (1.1 mL,1 equivalent), and stirred at 25° C. for 3 h. The reaction mixture wastreated with Example 1 (1.5 g, 1 equivalent) in 10 mL ofdichloromethane, triethylamine (2.0 mL, 3 equivalents), and stirred over72 h. The reaction was washed with water, dried over MgSO₄, filtered,and evaporated. This material was dissolved in tetrahydrofuran (20 mL)and treated with tetrabutylammonium fluoride (15.0 mL, 3 equivalents)for 2 h. at 25° C. Ethyl acetate was added and the reaction was washedwith 10% citric acid, water (2×), and brine. The reaction was dried overMgSO₄, filtered and concentrated to give 2.1 g (87.5%) of the titlecompound.

Example 639Ctert-butyl(1S,2R)-1-benzyl-3-{isobutyl[(3-nitro-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl]amino}-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639B (1.0 g, 1.86 mmol) in 10 mL of N,N-dimethylformamide wastreated with 2-(trimethylsilyl)ethoxymethyl chloride (1.30 mL, 4.0equivalents) and N,N-diisopropylethylamine (2.0 mL, 6 equivalents) at50° C. for 18 h. The reaction was diluted with ethyl acetate and washedwith water (2×) followed by brine. The organic layer was dried overMgSO₄, filtered, concentrated, and purified using 5% ethylacetate/dichloromethane to give 870 mg (58%) of the title compound.

Example 639Dtert-butyl(1S,2R)-3-[[(3-amino-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639C (800 mg, 1.0 mmol) was dissolved in 5 mL of ethyl acetateand treated with 20% Pd(OH)₂/C (200 mg, 0.28 equivalent) under hydrogenballoon pressure for 3 h. The reaction was filtered, concentrated andpurified using 5% ethyl acetate/chloroform to give 599 mg (78%) of thetitle compound.

Example 639Etert-butyl(1S,2R)-1-benzyl-3-{isobutyl[(3-{[(methylamino)sulfonyl]amino}-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl]amino}-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (100 mg, 0.13 mmol) in 1.3 mL of dichloromethane wastreated with pyridine (0.025 mL, 2.4 equivalents) and N-methyl sulfamoylchloride (ref: JOC 1976, 41, 4028)(0.014 mL, 1.2 equivalent) at 25° C.for 18 h. The reaction was concentrated and purified using 10% ethylacetate/chloroform to give 106 mg (95%) of the title compound.

Example 639FN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-{[(methylamino)sulfonyl]amino}benzenesulfonamide

Example 639E (25 mg, 0.03 mmol) was dissolved in methanol (0.22 mL) and4 N HCl (0.07 mL, 9.3 equivalents). The reaction was stirred at 25° C.for 18 h. The reaction was concentrated to give 15 mg (100%) of thetitle compound.

Example 640 ethyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamateExample 640Atert-butyl(1S,2R)-1-benzyl-3-[[(3-[(ethoxycarbonyl)amino]-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl](isobutyl)amino]-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (50 mg, 0.065 mmol) was dissolved in 0.7 mL ofdichloromethane and treated with pyridine (0.012 mL, 2.4 equivalents)and ethyl chloroformate (0.007 mL, 1.2 equivalents). The reaction wasstirred at 25° C. for 18 h, and the crude mixture was purified using 10%ethyl acetate/chloroform to give 49.6 (90%) of the title compound.

Example 640B ethyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamate

Example 640A (57 mg, 0.067 mmol) was dissolved in 0.75 mL of methanol,treated with 4 N HCl (0.25 mL, 15 equivalents) and stirred at 25° C. for2 h. The solvents were evaporated to yield 32 mg of the title compound(100%).

Example 641N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-(methylamino)benzenesulfonamideExample 641Atert-butyl(1S,2R)-1-benzyl-3-{isobutyl[(3-(methylamino)-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl]amino}-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (125 mg, 0.16 mmol) was dissolved in 1.8 mL of acetonitrileand treated with formaldehyde (0.065 mL, 5 equivalents), sodiumcyanoborohydride (20 mg, 2 equivalents), and acetic acid (0.018 mL, 2equivalents). The reaction was stirred for 18 h at 25° C., and the crudemixture was purified using 10% ethyl acetate/chloroform to give 39 mg(31%) of the title compound.

Example 641BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-hydroxy-N-isobutyl-3-(methylamino)benzenesulfonamide

Example 641A (36 mg, 0.05 mmol) was dissolved in 0.3 mL of methanol andtreated with 4 N HCl (0.3 mL, 24 equivalents). Stirring was continued at25° C. for 2 h. The reaction was concentrated to yield 21 mg of thetitle compound (100%).

Example 642N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(dimethylamino)-4-hydroxy-N-isobutylbenzenesulfonamideExample 642Atert-butyl(1S,2R)-1-benzyl-3-[[(3-(dimethylamino)-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl](isobutyl)amino]-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (125 mg, 0.16 mmol) was dissolved in 1.8 mL of acetonitrileand treated with formaldehyde (0.065 mL, 5 equivalents), sodiumcyanoborohydride (20 mg, 2 equivalents), and acetic acid (0.018 mL, 2equivalents). The reaction was stirred for 18 h. at 25° C. Purificationwas performed using 10% ethyl acetate/chloroform to give 54 mg (43%) ofthe title compound.

Example 642BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-(dimethylamino)-4-hydroxy-N-isobutylbenzenesulfonamide

Example 642A (54 mg, 0.07 mmol) was dissolved in 0.4 mL of methanol andtreated with 4 N HCl (0.4 mL, 23 equivalents). Stirring was continued at25° C. for 2 h. The reaction was concentrated to yield 30 mg of thetitle compound (100%).

Example 643N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(ethylamino)carbonyl]amino}-4-hydroxy-N-isobutylbenzenesulfonamideExample 643Atert-butyl(1S,2R)-1-benzyl-3-[[(3-{[(ethylamino)carbonyl]amino}-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl](isobutyl)amino]-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (50 mg, 0.065 mmol) was dissolved in 0.2 mL of toluene andtreated with ethyl isocyanate (0.1 mL, 20 equivalents). The reaction wasstirred at 50° C. for 18 h. Purification was performed using 10% ethylacetate/chloroform to give 35.3 (64%) of the title compound.

Example 643BN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-{[(ethylamino)carbonyl]amino}-4-hydroxy-N-isobutylbenzenesulfonamide

Example 643A (35 mg, 0.042 mmol) was dissolved in 0.25 mL of methanoland treated with 4 N HCl (0.25 mL, 24 equivalents). Stirring wascontinued at 25° C. for 2 h. The reaction was concentrated to yield 30mg of the title compound (100%).

Example 644 methyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamateExample 644Atert-butyl(1S,2R)-1-benzyl-3-{isobutyl[(3-[(methoxycarbonyl)amino]-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)sulfonyl]amino}-2-{[2-(trimethylsilyl)ethoxy]methoxy}propylcarbamate

Example 639D (57 mg, 0.074 mmol) was dissolved in 0.8 mL ofdichloromethane and treated with pyridine (0.014 mL, 2.4 equivalents)and methyl chloroformate (0.007 mL, 1.2 equivalents). The reaction wasstirred at 25° C. for 18 h. Purification was performed using 10% ethylacetate/chloroform to give 58.0 (95%) of the title compound.

Example 644B methyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamate

Example 644A (56 mg, 0.068 mmol) was dissolved in 0.3 mL of methanol andtreated with 4 N HCl (0.3 mL, 18 equivalents) and stirred at 25° C. for2 h. The reaction was concentrated to yield 31 mg of the title compound(100%).

Example 645 benzyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamateExample 645A benzyl5-{[((2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-{[2-(trimethylsilyl)ethoxy]methoxy}butyl)(isobutyl)amino]sulfonyl}-2-{[2-(trimethylsilyl)ethoxy]methoxy}phenylcarbamate

Example 639D (57 mg, 0.074 mmol) was dissolved in 0.8 mL ofdichloromethane and treated with pyridine (0.014 mL, 2.4 equivalents)and benzyl chloroformate (0.013 mL, 1.2 equivalents). The reaction wasstirred at 25° C. for 18 h. Purification was performed using 10% ethylacetate/chloroform to give 51.4 (78%) of the title compound.

Example 645B benzyl5-{[[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl](isobutyl)amino]sulfonyl}-2-hydroxyphenylcarbamate

Example 645A (49 mg, 0.056 mmol) was dissolved in 0.3 mL of methanol andtreated with 4 N HCl (0.3 mL, 21 equivalents). Stirring was continued at25° C. for 2 h. The reaction was concentrated to yield 30 mg (100%) ofthe title compound.

Example 6464-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-hydroxy-N-isobutylbenzenesulfonamidehydrate Example 646A 2-oxo-2,3-dihydro-1,3-benzoxazole-6-sulfonylchloride

Benzoxazolinone (13.5 g, 0.1 mol) was added slowly to a 0° C. solutionof chlorosulfonic acid (33.29 mL, 5 equivalents). The reaction waswarmed to 25° C. and stirred for 0.5 h, heated to 60° C. for 3 h. Thereaction was cooled to 25° C., poured into ice, filtered, and rinsedwith water. The resulting white solid was redissolved in 500 mL ofdiethyl ether and washed with water (2×), dried over Na₂SO₄, filteredand concentrated to 100 mL volume. Hexane was added (100 mL) and thewhite precipitate was filtered and placed under vacuum to yield 17 g(73%) of the title compound.

Example 646Btert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)sulfonyl]amino}propylcarbamate

Example 1 (200 mg, 0.6 mmol) was dissolved in 4 mL of dichloromethaneand treated with Example 646A (175 mg, 1.25 equivalents) andtriethylamine (0.21 mL, 2.5 equivalents). Stirring was maintained for 16h. at 25° C. The reaction was purified using 2% methanol/dichloromethaneto give 370 mg (58%) of the title compound.

Example 646C4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3-hydroxy-N-isobutylbenzenesulfonamide

Example 646B (370 mg, 0.694 mmol) was dissolved in 0.5 mL ofdichloromethane and treated with trifluoroacetic acid (1.7 mL). Thereaction was stirred for 3 h at 25° C., quenched with 50 mL of water,and made alkaline to pH=9 with sodium bicarbonate. Extract with ethylacetate, filter off the precipitate, dry the organic layer over Na₂SO₄,filter, and concentrate to give 290 mg of the intermediate. A portion ofthis material (120 mg, 0.23 mmol) was dissolved in 1 mL of methanol,treated with 3 mL of 30% NaOH solution, and heated to 80° C. for 3 h.The solvents were evaporated and the crude residue was extracted withethyl acetate. The material was purified using 10%methanol/dichloromethane (w/1% NH₄OH) to yield 67 mg (60%) of the titlecompound.

Example 647N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-(2-hydroxyethyl)-N-isobutylbenzenesulfonamideExample 647Atert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-vinylphenyl)sulfonyl]amino}propylcarbamate

Example 1 (2.27 g, 6.8 mmol) in 20 mL of dichloromethane at 25° C. wastreated with triethylamine (3.75 mL, 4 equivalents) followed by dropwiseaddition of 4-vinylbenzene sulfonyl chloride (1.6 g, 1.2 equivalents).Stirring was continued for 16 h. after which the reaction was quenchedwith 1 N NaHCO₃, and evaporated. The material was purified using 20%ethyl acetate/hexane to give 1.5 g (44%) of the title compound.

Example 647Btert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-(2-hydroxyethyl)phenyl]sulfonyl}(isobutyl)amino]propylcarbamate

Example 647A (100 mg, 0.2 mmol) was dissolved in 3 mL of tetrahydrofuranat 0° C. and treated with borane-methyl sulfide complex (2M/tetrahydrofuran, 0.3 mL, 3 equivalents). Stirring was continued for 3h after which water (0.8 mL), followed by an aqueous solution of 1N NaOH(0.3 ml) was added. The reaction allowed to warm to 25° C. and 30% H₂O₂(0.2 mL) was added. After stirring for 30 min., the reaction waspartitioned between brine and ethyl acetate. The organic layer wasconcentrated and the material was purified using 40% ethylacetate/hexanes to give 45 mg (43.5%) of the title compound.

Example 647CN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-4-(2-hydroxyethyl)-N-isobutylbenzenesulfonamide

Example 647B (37 mg, 0.0712 mmol) was dissolved in 0.2 mL ofdichloromethane and treated with 0.8 mL of trifluoroacetic acid andstirred at 25° C. for 3 h. The reaction was evaporated and purifiedusing 5% methanol/dichloromethane (w/0.5% NH₄OH) to give 16 mg (53.5%)of the title compound.

Example 648N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-[(methylsulfonyl)amino]benzenesulfonamideExample 648Atert-butyl(1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-nitrophenyl)sulfonyl]amino}propylcarbamate

Example 1 (400 mg, 1.2 mmol) was dissolved in 8 mL of dichloromethaneand treated with p-nitro benzenesulfonyl chloride (0.316 g, 1.2equivalents) and triethylamine (0.414 mL, 2.5 equivalents). The reactionwas stirred at 25° C. for 16 h, and purified using 2%methanol/dichloromethane to give 0.56 g (90%) of the title compound.

Example 648Btert-butyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate

Example 648A (0.56 g, 1.07 mmol) in 10 mL of ethyl acetate was treatedwith 20% Pd(OH)₂/C (0.35 g, 0.2 equivalent) under a hydrogen balloonatmosphere for 2 h. The reaction was filtered, evaporated, and purifiedusing 5% methanol/dichloromethane to give 520 mg (98%) of the titlecompound.

Example 648CN-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-isobutyl-4-[(methylsulfonyl)amino]benzenesulfonamide

Example 648B (150 mg, 0.3 mmol) in 0.5 mL of dichloromethane was treatedwith pyridine (0.5 mL, 20 equivalents) and methanesulfonyl chloride(0.06 mL, 2.2 equivalents) at 25° C. for 5 h. The reaction was quenchedwith 1 N NaHCO₃, diluted with dichloromethane, concentrated, andpurified using 1% methanol/20% ethyl acetate/dichloromethane to give 150mg (87%) of product. This material was dissolved in 0.2 mL ofdichloromethane and treated with 0.5 ml, of trifluoroacetic acid at 25°C. for 3 h. The reaction was quenched with 10 mL of water, made alkalinewith 1 N NaHCO₃ and extracted with ethyl acetate. This material waspurified using 5% methanol/dichloromethane (w/1% NH₄OH) to give 109 mg(88%) of the title compound.

Example 649(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 143 (59 mg, 0.198 mmol) was combined with N-hydroxysuccinimide(25 mg, 1.1 equivalents) and DCC (45 mg, 1.1 equivalents) indichloromethane (1 mL) and stirred for 1 h at 25° C. The solids arefiltered, and to this mixture is added N-methylmorpholine (22 μL, 1equivalent) and Example 625B (100 mg, 1 equivalent). The mixture wasstirred for 16 h, evaporated, and purified using 1.5% methanol/CHCl₃ togive 42 mg (32%) of the title compound. ¹H NMR (300 MHz, CDCl₃) δ ppm0.74 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78 Hz, 3H), 0.90 (m, 6H), 1.86(dd, J=13.90, 7.12 Hz, 1H), 2.13 (m, 1H), 2.69 (s, 3H), 2.79 (m, 2H),2.94 (dd, J=7.46, 2.71 Hz, 2H), 2.99 (m, 1H), 3.04 (d, J=3.73 Hz, 1H),3.10 (d, J=8.48 Hz, 1H), 3.16 (dd, J=8.82, 4.41 Hz, 1H), 3.24 (m, 2H),3.59 (d, J=10.85 Hz, 1H), 3.78 (m, 1H), 3.85 (d, J=3.05 Hz, 1H), 4.04(dd, J=9.49, 5.09 Hz, 1H), 4.42 (s, 2H), 6.44 (d, J=8.82 Hz, 1H), 6.92(m, 2H), 6.96 (s, 1H), 7.17 (m, 5H), 7.65 (m, 2H).

The compounds listed in Table 16, wherein X₇, X₉, and X₄ representrespectively the points of connection to the core structure (M), wereprepared by coupling the corresponding acids (Examples 31-160) with thecorresponding amines (Examples 625-648) as exemplified in Example 362(Method A), Example 162 (Method B), Example 524 (Method C) and Example478 (Method D).

TABLE 16

Ex. Method R₉ R₇ R₄ 650 C

651 C

652 C

653 C

654 C

655 C

656 C

657 C

658 C

659 C

660 C

661 C

662 C

663 C

664 C

665 A

666 A

667 C

668 C

669 C

670 C

671 C

672 A

673 A

674 A

675 A

676 A

677 A

678 A

679 C

680 C

681 A

682 A

683 A

684 A

685 A

686 A

687 A

688 C

689 C

690 C

691 C

692 C

693 A

694 A

695 A

696 A

697 A

698 A

699 A

700 A

701 A

702 A

703 B

704 A

705 B

706 B

707 A

708 A

709 A

710 D

Example 711(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({4-[(E)-(hydroxyimino)methyl]phenyl}sulfonyl)(neopentyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 143D (64 mg, 0.21 mmol) was dissolved in N,N-dimethylformamide(3 mL) and treated with EDAC (66.3 mg, 2 equivalents), HOBT (58 mg, 2equivalents), Example 26 (111 mg, 1.2 equivalents), andN-methylmorpholine (47 μL, 2 equivalents) at 25° C. for 16 h. Thesolvents were evaporated and the crude residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 73 mg (47%) ofthe title compound.

Example 712(2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExample 712A(2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 270 (127 mg, 0.18 mmol) was dissolved in dichloromethane (1.8mL) and treated with Boc-β-alanine hydroxysuccinimide ester (75 mg, 1.4equivalents), N-methylmorpholine (40 μL, 2 equivalents) and DMAP (30 mg,1.4 equivalents) at 25° C. for 18 h. The solvents were evaporated andthe crude residue was purified by HPLC reverse phase chromatographyusing water (0.1% trifluoroacetic acid):acetonitrile (95:5) toacetonitrile (100%) to give 123 mg (78%) of the title compound.

Example 712B(2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 712A (150 mg, 0.17 mmol) was dissolved indichloromethane:trifluoroacetic acid (3 mL, 2:1) at 25° C. for 30 min.The solvents were evaporated and the crude residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 76 mg (50%) ofthe title compound.

Example 713(2S)—N-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExample 713A (2R,3S)-3-amino-1-(isobutylamino)-4-phenyl-2-butanol

Example 1 (3 g, 8.9 mmol) in dichloromethane (2 mL) was treated withtrifluoroacetic acid (8 mL, 12 equivalents) and stirred for 5 h at 25°C. The mixture was quenched with water (50 mL), the aqueous layer wasmade alkaline to pH 9 with NaHCO₃. The mixture was stirred for 3 h, andthe solids were filtered and dried in vacuo to give 2.5 g (100%) of thediamine.

Example 713B(2S)—N-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 143D (1 g, 3.4 mmol) was combined with the Example 713A (1.5 g,1.5 equivalents) in N,N-dimethylformamide (50 mL) and to this mixturewas added HOBT (0.6 g, 1.5 equivalents) and EDAC (0.86 g, 1.5equivalents). The mixture was stirred for 16 h at 25° C. and quenchedwith NaHCO₃, extracted with ethyl acetate, and evaporated. The residuewas purified using 10% methanol/dichloromethane to give 1.14 g (74%) ofthe title compound.

Example 714(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(3-methoxyphenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 713B (20 mg, 0.04 mmol) was dissolved in dichloromethane (0.5mL) and treated with triethylamine (13.7 μL, 2.5 equivalents) followedby 3-methoxybenzene sulfonyl chloride (9.8 mg, 1.2 equivalents) at 25°C. for 16 h. The solvents were evaporated, and the residue was purifiedusing chloroform to give 20.2 mg (76%) of the title compound. ¹H NMR(300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78 Hz, 3H),0.87 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.55 (s, 1H), 1.84 (m,1H), 2.13 (m, 1H), 2.69 (s, 3H), 2.84 (dd, J=13.56, 6.78 Hz, 1H), 3.01(m, 1H), 3.13 (m, 1H), 3.22 (m, 1H), 3.63 (d, J=11.19 Hz, 1H), 3.76 (m,1H), 3.83 (d, J=3.05 Hz, 1H), 3.86 (d, J=5.09 Hz, 3H), 4.16 (m, 1H),4.41 (m, 2H), 6.45 (d, J=8.82 Hz, 1H), 6.92 (d, J=6.10 Hz, 1H), 7.09 (m,1H), 7.12 (m, 1H), 7.15 (d, J=3.73 Hz, 1H), 7.19 (m, 5H), 7.31 (m, 2H),7.38 (m, 2H), 7.43 (m, 1H).

The compounds listed in Table 17, wherein X₄ represents the point ofconnection to the core structure (N), were prepared using the procedureas exemplified in Example 714, substituting the corresponding sulfonylchlorides for 3-methoxybenzene sulfonyl chloride:

TABLE 17 N

Ex. R₄ 715

716

717

718

719

720

721

722

723

724

725

726

727

728

729

730

731

732

733

734

735

736

737

738

739

740

741

742

743

744

745

746

747

748

749

750

751

752

753

754

755

756

757

758

759

760

Example 761(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(3-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 714 (31 mg, 0.045 mmol) in dichloromethane (3 mL) was added BBr₃(20 μL, equivalents) and stirred for 2 h at 25° C. The mixture wasquenched with 1N NaHCO₃ and extracted with ethyl acetate. The solventswere evaporated and the residue was purified using ethyl acetate to give21 mg (69%) of the title compound.

Example 762(2S)—N-{(1S,2R)-1-benzyl-3-[[(5-bromo-2-hydroxyphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

In a similar manner to Example 761, Example 747 was treated with BBr₃ togive the title compound.

Example 763(2S)—N-{(1S,2R)-1-benzyl-3-[{[4-(1,2-dihydroxyethyl)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 749 (30 mg, 0.044 mmol) dissolved in tetrahydrofuran (1 mL) andwater (0.2 mL) was added 4% weight OsO₄ in water (16.3 μL, 6 mol %) andNMMO (5.2 mg, 1.2 equivalents). The mixture was stirred at 25° C. for 4h and quenched with 10% NaHSO₃. The mixture was extracted with ethylacetate, the solvents were evaporated, and the residue was purifiedusing 5% methanol/dichloromethane to give 21 mg (67%) of the titlecompound.

Example 764(2S)—N-{(1S,2R)-1-benzyl-3-[[(4-formylphenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 749 (81 mg, 0.12 mmol) in tetrahydrofuran (3 mL) and water (0.6mL) was added 4% weight OsO₄ in water (44 μL, 6 mol %) followed byNaIO₄(56 mg, 2.2 equivalents). The mixture was stirred at 25° C. for 16h and quenched with 10% NaHSO₃, extracted with ethyl acetate, solventswere evaporated, and the residue was purified using ethyl acetate togive 68 mg (84%) of the title compound.

Example 765

(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[4-(hydroxymethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 764 (14 mg, 0.02 mmol) was dissolved in ethanol (0.5 mL) andcombined with NaBH₄ (2.2 mg, 3 equivalent) and stirred at 25° C. for 1h. The solvents were evaporated, and the residue was purified using 5%methanol/dichloromethane to give 9 mg (69%) of the title compound.

Example 766(2S)—N-{(1S,2R)-1-benzyl-3-[{[4-(formylamino)phenyl]sulfonyl}(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 650 (10 mg, 0.014 mmol) was dissolved in tetrahydrofuran (0.25mL) and combined with formic acetic anhydride (2 drops) and the mixturewas stirred for 1 h. The solvent was evaporated, and the residue waspurified by using 5% methanol/dichloromethane to give 8.5 mg (83%) ofthe title compound.

Example 767(2S)—N-{(1S,2R)-3-[[(3-amino-4-chlorophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-2-(3-{[2-(hydroxymethyl)-1,3-thiazol-4-yl]methyl}-2-oxo-1-imidazolidinyl)-3-methylbutanamide

Example 687 (45 mg, 0.059 mmol) was dissolved in water:tetrahydrofuran(1 mL, 2:1) and treated with lithium hydroxide (8 mg, 3 equivalents) at25° C. for 30 min. The mixture was neutralized with 1N HCl (0.2 mL) andextracted with ethyl acetate. The organic layer was separated and washedwith water, brine, dried over magnesium sulfate and the solvents wereevaporated to give 43 mg (100%) of the title compound.

Example 768(2S)—N-{(1S,2R)-3-[{[3-(acetylamino)-4-hydroxyphenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExample 768A(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxy-3-nitrophenyl)sulfonyl](isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

To 4-hydroxy-3-nitrobenzenesulfonyl chloride (69 mg, 0.27 mmol) indichloromethane (1.2 mL) was added bistrimethylsilylacetamide (72 μL, 1equivalent) at 25° C. for 3 h. To this mixture was added the Example713B (150 mg, 1 equivalent) followed by triethylamine (0.12 mL, 3equivalents). The mixture was stirred for 16 h, and the solvents wereevaporated. The crude residue was treated with tetrabutylammoniumfluoride (TBAF) (0.9 mL, 3 equivalents 1M tetrabutyl ammoniumfluoride/tetrahydrofuran) for 2 h and the solvents were evaporated. Theresidue was purified by HPLC reverse phase chromatography using water(0.1% trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%)to give 132 mg (62%) of the title compound.

Example 768B(2S)—N-{(1S,2R)-3-[[(3-amino-4-hydroxyphenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 768A (132 mg, 0.184 mmol) in ethanol/acetic acid (2 mL, 1:1) isadded Fe powder (40 mg, 4 equivalents) at 70° C. for 2 h. The mixturewas evaporated and partitioned between CHCl₃ and 10% EDTA disodium salt.The organic layer was washed with brine, dried over MgSO₄, filtered, andevaporated to give 112 mg (90% crude yield) of the title compound.

Example 768C(2S)—N-{(1S,2R)-3-[{[3-(acetylamino)-4-hydroxyphenyl]sulfonyl}(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 768B (20 mg, 0.029 mmol) was dissolved in dichloromethane (0.3mL) and treated with pyridine (2 μL, 1 equivalent) and acetyl chloride(1.2 μL, 0.6 equivalent) at 25° C. for 1 h. The mixture was quenchedwith methanol, and the solvents were evaporated. The residue waspurified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give16.9 mg (75%) of the title compound.

The compounds listed in Table 18, wherein X_(4a), represents the pointsof connection to the core structure (O), were prepared by coupling thecorresponding activated acylating agents with Example 768B:

TABLE 18 O

Ex# R_(4a) 769

770

771

772

Example 773(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl({4-[(methoxyimino)methyl]phenyl}sulfonyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 764 (14.7 mg, 0.022 mmol) was dissolved in ethanol (0.5 mL) andtreated with N,N-diisopropylethylamine (6.1 μL, 2.2 equivalents) andhydroxylamine-O-methyl ether hydrochloride (3.6 mg, 2 equivalents) at25° C. for 2 h. The mixture was partitioned between 1N NaHCO₃ and ethylacetate. The organic layer was evaporated, and the residue was purifiedusing 5% methanol/chloroform to give 7.1 mg (46%) of the title compound.

Example 774(2S)—N-{(1S,2R)-1-benzyl-3-[(2,3-dihydro-1H-indol-5-ylsulfonyl)(isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 693 (25 mg, 0.034 mmol) was dissolved in methanol (2 mL) andtreated with 1N HCl (3 mL) at 60° C. for 5 h. The solvents wereevaporated, and the residue was purified using 5%methanol/dichloromethane to give 12 mg (51%) of the title compound.

Example 775(2S)—N-{(1S,2R)-3-[[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 755 was treated in a similar manner to Example 774 to give thetitle compound.

Example 776(2S)—N-{(1S,2R)-3-[({3-[(3-aminopropanoyl)amino]-4-hydroxyphenyl}sulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 772 (10 mg, 0.012 mmol) was dissolved in dichloromethane (0.2mL) and trifluoroacetic acid (0.1 mL), and the mixture was stirred at25° C. for 1 h. The solvents were evaporated, and the residue waspurified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give8 mg (79%) of the title compound.

Example 777 tert-butyl2-(3-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}anilino)-2-oxoethylcarbamateExample 777A(2S)—N-((1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(3-nitrophenyl)sulfonyl]amino}propyl)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 713B (50 mg, 0.097 mmol) was dissolved in dichloromethane (1 mL)and treated with 3-nitrobenzenesulfonyl chloride (26 mg, 1.2equivalents) and triethylamine (27 μL, 2 equivalents) at 25° for 18 h.The solvents were evaporated and the crude residue was purified usingchloroform-chloroform/2% methanol to give 66.8 mg (97%) of the titlecompound.

Example 777B tert-butyl2-(3-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-(3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl)(isobutyl)amino]sulfonyl}anilino)-2-oxoethylcarbamate

Example 777A (66 mg, 0.094 mmol) was dissolved in ethanol:acetic acid (1mL, 1:1) and treated with iron powder (21 mg, 4 equivalents) at 70° C.for 1.5 h. The mixture was diluted with chloroform and washed twice with10% EDTA disodium salt. The aqueous layers were reextracted withchloroform, the organic layers combined, washed with brine, dried overmagnesium sulfate, and the solvents were evaporated to give crudeproduct amine. This amine was dissolved in dichloromethane (1 mL) andtreated with Boc-glycine N-Hydroxysuccinimide ester (38 mg, 1.5equivalents) and pyridine (0.011 mL, 1.5 equivalents) and stirred at 25°C. for 18 h. The solvents were evaporated, and the crude residue waspurified by HPLC reverse phase chromatography using water (0.1%trifluoroacetic acid):acetonitrile (95:5) to acetonitrile (100%) to give35.3 mg (45%) of the title compound.

Example 778(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[{[3-(hydroxymethyl)phenyl]sulfonyl}(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 758 (88 mg, 0.123 mmol) was dissolved in dichloromethane (1 mL)and treated with diisobutyl aluminum hydride (0.62 mL, 5 equivalents, 1Msolution in dichloromethane) at −78° C. for 1 h. The mixture wasquenched with acetone (0.1 mL), warmed to 25° C., and partitionedbetween dichloromethane and saturated Rochelle's salt solution. Afterstirring for 1 h, the organic layer was separated, dried over Na₂SO₄,filtered, and evaporated, and the residue was purified using ethylacetate to give 68 mg (80%) of the title compound.

Example 779(2S)—N-{(1S,2R)-1-benzyl-3-[[(5-formyl-2-furyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 757 (103 mg, 0.134 mmol) in acetonitrile (1 mL) at 0° C. wasadded trimethylsilyl iodide (0.2 mL, 10 equivalents). The mixture waswarmed to 25° C. for 2 h, partitioned between ethyl acetate and NaS₂O₃,and the organic layer was separated. The layer was dried over Na₂SO₄ andevaporated. The residue was purified using ethyl acetate to give 35 mg(39%) of the title compound.

Example 780(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({5-[(E)-(hydroxyimino)methyl]-2-furyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExample 780A(2S)—N-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutyl{[5-({[(4-nitrobenzyl)oxy]imino}methyl)-2-furyl]sulfonyl}amino)propyl]-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 713B (50 mg, 0.097 mmol) in dichloromethane (0.5 mL) was treatedwith triethylamine (30 μL, 2 equivalents) followed by5-(p-nitrobenzyloxyimino)-2-furan sulfonyl chloride (40 mg, 1.2equivalents) at 25° C. for 16 h. The solvents were evaporated, and theresidue was purified using ethyl acetate:hexanes (3:1) to give 63 mg(79%) of the title compound.

Example 780B(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({5-[(E)-(hydroxyimino)methyl]-2-furyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamideExamples 781(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[({5-[(Z)-(hydroxyimino)methyl]-2-furyl}sulfonyl)(isobutyl)amino]propyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanamide

Example 780A (60 mg, 0.073 mmol) was dissolved in ethanol:acetic acid(1:1) (1 mL), treated with iron powder (20 mg, 5 equivalents) and heatedat 70° C. for 4 h. The mixture was cooled, evaporated, and partitionedbetween CHCl₃ and 10% EDTA. The organic layer was dried over Na₂SO₄,filtered, and evaporated. The residue was purified using ethylacetate:hexanes (3:1) to give 11 mg (22%) of Example 780B and 12 mg(24%) of Example 781.

Example 782(2S)—N-{(1S,2R)-3-[({4-[amino(hydroxyimino)methyl]phenyl}sulfonyl)(isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxoimidazolidin-1-yl}butanamideExample 7834-{[{(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2-oxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}(isobutyl)amino]sulfonyl}benzamide

Example 721 (33 mg, 0.048 mmol) was dissolved in ethanol (1 mL) andtreated with triethylamine (70 μL, 10 equivalents) and hydroxylaminehydrochloride (14 mg, 4 equivalents). The mixture was heated at 50° C.for 3 hrs. The solvents were evaporated, and the residue was purifiedusing 5% methanol/dichloromethane to give 13 mg (37%) of Example 782 and8.5 mg (25%) of Example 783.

Example 7844-{[[(2R,3S)-2-hydroxy-3-({(2S,3S)-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanoyl}amino)-4-phenylbutyl](isobutyl)amino]sulfonyl}benzamide

Example 785 (36 mg, 0.053 mmol) was dissolved in methanol (1 mL) andtreated with triethylamine (75 μL, 10 equivalents) and hydroxylaminehydrochloride (15 mg, 4 equivalents). The mixture was heated to 80° C.for 1 h. The solvents were evaporated, and the residue was purifiedusing 8% methanol/ethyl acetate to give 20 mg (53%) of thep-hydroxyamidine and 4 mg (11%) of the title compound.

Example 785(2S,3S)—N-{(1S,2R)-1-benzyl-3-[[(4-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamideExample 785A(2S,3S)—N-[(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide

Example 103 (0.266 g, 0.9 mmol) was combined with Example 713A (0.153 g,1 equivalent) in N,N-dimethylformamide (2 mL) and to this mixture wasadded HOBT (0.1 g, 1.5 equivalents) and EDAC (0.15 g, 1.5 equivalents).The mixture was stirred for 16 h at 25° C. and quenched with NaHCO₃,extracted with ethyl acetate, and evaporated under vacuum. The residuewas purified using 10% methanol/dichloromethane/0.5% NH₄OH to give 50 mg(19%) of the amine.

Example 785B(2S,3S)—N-{(1S,2R)-1-benzyl-3-[[(4-cyanophenyl)sulfonyl](isobutyl)amino]-2-hydroxypropyl}-3-methyl-2-[2-oxo-3-(3-pyridinylmethyl)-1-imidazolidinyl]pentanamide

Example 785A (50 mg, 0.098 mmol) was dissolved in dichloromethane (1 mL)and combined with p-cyanobenzenesulfonyl chloride (24 mg, 1.2equivalents) and triethylamine (41 μL, 3 equivalents) at 25° C. for 16h. The mixture was quenched with 1N NaHCO₃ and extracted with ethylacetate. The organic layer was evaporated, and the residue was purifiedusing ethyl acetate to give 49 mg (74%) of the title compound.

Example 786(2S)—N-{(1S,2R)-1-benzyl-2-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](isobutyl)amino]propyl}-2-{3-[(2-ethyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}-3-methylbutanamide

Example 290 (75 mg, 0.23 mmol) was combined with N-hydroxysuccinimide(24.8 mg, 1.1 equivalents) and DCC (44.5 mg, 1.1 equivalents) indichloromethane (1 mL) and stirred for 1 h at 25° C. The solids arefiltered, and to this mixture was added N-methylmorpholine (24 μL, 1equivalent) and 625B (77 mg, 1 equivalent). The mixture was stirred for16 h, evaporated, and was purified using 1% methanol/CHCl₃ to give 54 mg(40%) of the title compound. ¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (t,J=6.61 Hz, 6H), 0.88 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.32(t, J=7.63 Hz, 3H), 1.77 (d, J=10.17 Hz, 1H), 1.83 (m, 1H), 2.07 (m,1H), 2.66 (dd, J=14.24, 10.85 Hz, 1H), 2.83 (dd, J=13.56, 6.78 Hz, 1H),2.98 (m, 2H), 3.03 (m, 1H), 3.17 (m, 1H), 3.27 (d, J=17.97 Hz, 1H), 3.61(d, J=17.97 Hz, 1H), 3.85 (m, 2H), 3.89 (d, J=11.19 Hz, 1H), 4.19 (m,1H), 4.75 (m, 2H), 6.33 (d, J=9.49 Hz, 2H), 6.93 (d, J=8.82 Hz, 2H),7.04 (s, 1H), 7.07 (s, 5H), 7.66 (m, 2H).

The compounds listed in Table 19, wherein X₇, X₁₁, X₄ representrespectively the points of connection to the core structure (P), wereprepared by coupling the corresponding acids (Examples 287-359) with theamines (Examples 625-648), as exemplified in Example 362 (Method A),Example 162 (Method B) and Example 524 (Method C):

TABLE 19

Ex. Method R₁₁ R₇ R₄ 787 C

788 C

789 C

790 C

791 C

792 C

793 C

794 C

795 A

796 A

797 A

798 A

800 A

801 A

802 A

803 A

804 B

805 B

806 A

807 A

808 A

809 A

810 A

811 A

812 A

813 A

814 A

815 A

816 A

817 A

818 A

819 A

820 A

821 A

822 A

823 A

824 A

825 A

826 A

827 A

828 A

829 A

830 A

831 A

832 A

833 B

834 A

835 A

836 A

837 A

838 A

839 A

840 A

841 A

842 B

843 A

Example 844(2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(cyclopentylmethyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamideExample 844A tert-butyl3-{[((E)-{4-[((cyclopentylmethyl){(2R,3S)-2-hydroxy-3-[((2S)-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanoyl)amino]-4-phenylbutyl}amino)sulfonyl]phenyl}methylidene)amino]oxy}-3-oxopropylcarbamate

Example 372 (78 mg, 0.1 mmol) was dissolved in dichloromethane (1 mL)and treated with Boc-β-alanine hydroxysuccinimide ester (45 mg, 1.4equivalents), N-methylmorpholine (25 μL, 2 equivalents) and DMAP (20 mg,1.4 equivalents) at 25° C. for 18 h. The solvents were evaporated andthe crude residue was purified by HPLC reverse phase chromatographyusing water (0.1% trifluoroacetic acid):acetonitrile (95:5) toacetonitrile (100%) to give 62 mg (65%) of the title compound.

Example 844B(2S)—N-{(1S,2R)-3-[{[4-((E)-{[(3-aminopropanoyl)oxy]imino}methyl)phenyl]sulfonyl}(cyclopentylmethyl)amino]-1-benzyl-2-hydroxypropyl}-3-methyl-2-{3-[(2-methyl-1,3-thiazol-4-yl)methyl]-2,4-dioxo-1-imidazolidinyl}butanamide

Example 844A (60 mg, 0.066 mmol) was dissolved indichloromethane:trifluoroacetic acid (3 mL, 2:1) at 25° C. for 30 min.The solvents were evaporated and the crude residue was purified by HPLCreverse phase chromatography using water (0.1% trifluoroaceticacid):acetonitrile (95:5) to acetonitrile (100%) to give 46 mg (75%) ofthe title compound.

NMR Data Example 163

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.53 (s, 1H),1.85 (m, 1H), 2.17 (m, 1H), 3.00 (m, 9H), 3.66 (d, J=10.85 Hz, 1H), 3.77(d, J=3.39 Hz, 1H), 3.82 (m, 1H), 4.16 (d, J=15.26 Hz, 1H), 4.23 (m,1H), 4.40 (d, J=15.60 Hz, 1H), 6.45 (d, J=9.16 Hz, 1H), 7.19 (m, 5H),7.33 (d, J=1.70 Hz, 1H), 7.71 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz,2H), 8.16 (s, 1H)

Example 164

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (t, J=6.27 Hz, 6H), 0.82 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 1.39 (d, J=9.83 Hz, 1H), 1.75 (dd,J=14.24, 6.78 Hz, 1H), 2.12 (m, 1H), 2.62 (dd, J=14.41, 10.34 Hz, 1H),2.80 (dd, J=13.56, 6.78 Hz, 1H), 3.05 (m, 3H), 3.30 (m, 1H), 3.30 (m,1H), 3.54 (d, J=10.85 Hz, 1H), 3.59 (d, J=2.71 Hz, 1H), 3.70 (m, 1H),3.94 (m, 2H), 4.21 (m, 1H), 5.92 (d, J=9.49 Hz, 1H), 7.13 (dd, J=6.44,2.71 Hz, 2H), 7.24 (m, J=3.73 Hz, 3H), 7.33 (d, J=4.07 Hz, 1H), 7.54 (t,J=7.12 Hz, 1H), 7.66 (d, J=8.48 Hz, 2H), 7.70 (d, J=8.82 Hz, 2H), 7.77(d, J=10.85 Hz, 2H), 8.15 (s, 1H), 8.18 (d, J=8.48 Hz, 1H), 8.39 (s,1H), 8.99 (d, J=4.41 Hz, 1H)

Example 165

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.44Hz, 9H), 1.89 (m, 1H), 2.22 (s, 3H), 3.01 (m, 11H), 3.61 (d, J=10.51 Hz,1H), 3.95 (s, 1H), 4.20 (m, 2H), 4.35 (s, 2H), 6.72 (s, 1H), 6.93 (m,1H), 7.18 (m, 5H), 7.69 (d, J=8.48 Hz, 2H), 7.79 (d, Hz, 2H), 8.16 (s,1H)

Example 166

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.44 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 2.05 (m, 2H), 2.52 (dd, J=13.90, 11.53Hz, 1H), 2.68 (m, 1H), 2.97 (s, 6H), 3.15 (m, 7H), 3.47 (dd, J=14.58,3.73 Hz, 1H), 3.75 (m, 2H), 4.11 (s, 1H), 4.40 (d, J=15.60 Hz, 1H), 4.63(d, J=16.28 Hz, 1H), 4.69 (s, 2H), 7.16 (m, 5H), 7.57 (s, 1H), 7.78 (d,J=8.48 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H), 7.95 (d, J=9.83 Hz, 1H), 8.14(s, 1H)

Example 167

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.44 Hz, 6H), 1.75 (m, 4H),2.00 (m, 4H), 2.56 (m, 4H), 2.69 (s, 3H), 3.22 (m, 7H), 3.74 (m, 2H),4.12 (m, 1H), 4.42 (s, 2H), 7.13 (m, 5H), 7.78 (d, J=8.82 Hz, 2H), 7.84(d, J=8.82 Hz, 2H), 7.97 (d, J=9.49 Hz, 1H), 8.14 (s, 1H)

Example 168

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (m, 6H), 1.57 (m, 1H), 1.89 (m, 2H),2.01 (m, 2H), 2.55 (m, 2H), 2.69 (d, J=1.36 Hz, 3H), 3.12 (m, 6H), 3.42(m, J=14.92, 3.05 Hz, 1H), 3.59 (m, 1H), 3.79 (m, 4H), 4.13 (m, 2H),4.42 (s, 2H), 7.11 (m, 5H), 7.20 (d, J=2.37 Hz, 1H), 7.77 (d, J=7.80 Hz,2H), 7.83 (t, J=2.03 Hz, 2H), 7.93 (t, J=10.17 Hz, 1H), 8.14 (s, 1H)

Example 169

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.79 (d, J=6.78Hz, 3H), 2.03 (m, 1H), 2.52 (m, 2H), 2.70 (s, 3H), 2.76 (dd, J=15.09,10.00 Hz, 1H), 3.02 (d, J=12.89 Hz, 6H), 3.15 (m, 6H), 3.57 (m, 2H),3.75 (d, J=11.19 Hz, 1H), 4.00 (m, 3H), 4.42 (s, 2H), 7.12 (m, 5H), 7.20(s, 1H), 7.84 (d, J=8.82 Hz, 2H), 7.90 (d, J=8.82 Hz, 2H), 8.06 (d,J=9.83 Hz, 1H), 8.16 (s, 1H)

Example 170

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=2.71 Hz, 3H), 0.79 (m, 3H),1.23 (m, 1H), 1.61 (m, 5H), 2.04 (m, 1H), 2.26 (dd, J=15.09, 7.29 Hz,1H), 2.52 (m, 1H), 2.70 (s, 3H), 3.13 (m, 11H), 3.46 (dd, J=14.92, 3.73Hz, 1H), 3.72 (d, J=0.85 Hz, 1H), 3.77 (m, 1H), 4.12 (m, 1H), 4.42 (d,J=1.36 Hz, 2H), 7.08 (m, 3H), 7.14 (m, 2H), 7.21 (s, 1H), 7.78 (d,J=8.82 Hz, 2H), 7.83 (d, J=8.82 Hz, 2H), 7.96 (m, 1H)

Example 171

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.76 (d, J=6.78Hz, 3H), 2.02 (m, 1H), 2.51 (m, 2H), 2.69 (d, J=4.07 Hz, 3H), 3.12 (m,2H), 3.35 (s, 3H), 3.42 (m, 1H), 3.70 (d, J=11.19 Hz, 1H), 3.79 (m, 1H),4.09 (s, 1H), 4.41 (m, 2H), 4.64 (s, 2H), 6.20 (d, J=3.39 Hz, 1H), 6.25(m, 1H), 7.08 (m, 3H), 7.15 (m, 2H), 7.20 (s, 1H), 7.25 (d, J=2.71 Hz,1H), 7.71 (m, 4H), 7.95 (d, J=9.83 Hz, 1H), 8.12 (s, 1H)

Example 172

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (t, J=6.44 Hz, 6H), 2.05 (m, 1H),2.48 (dd, J=13.90, 11.19 Hz, 1H), 2.56 (m, 1H), 2.69 (s, 3H), 3.16 (m,8H), 3.70 (m, 1H), 3.75 (s, 1H), 3.78 (m, 1H), 4.03 (m, 1H), 4.41 (d,J=2.37 Hz, 2H), 4.64 (d, J=17.63 Hz, 1H), 4.91 (d, J=17.63 Hz, 2H), 7.10(m, 5H), 7.20 (s, 1H), 7.83 (m, 4H), 8.00 (d, J=8.14 Hz, 1H), 8.17 (s,1H)

Example 173

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.79 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.87 (m, 1H),2.14 (m, 1H), 2.41 (s, 3H), 2.61 (s, 3H), 2.70 (m, 1H), 2.88 (dd,J=13.56, 6.78 Hz, 1H), 2.98 (m, 1H), 3.13 (m, 7H), 3.62 (d, J=11.19 Hz,1H), 3.77 (m, 1H), 4.11 (m, 1H), 4.38 (d, J=4.07 Hz, 2H), 6.48 (d,J=9.16 Hz, 1H), 7.16 (m, 5H), 7.70 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48Hz, 2H), 8.15 (s, 1H)

Example 174

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.44 Hz, 3H), 0.86 (t, J=6.44Hz, 6H), 0.91 (d, J=6.78 Hz, 3H), 1.53 (d, J=5.09 Hz, 1H), 1.87 (m,J=6.44 Hz, 1H), 2.18 (m, 1H), 2.82 (m, 3H), 3.09 (m, 5H), 3.69 (d,J=11.19 Hz, 1H), 3.79 (m, 2H), 4.22 (m, 1H), 4.30 (d, J=15.60 Hz, 1H),4.54 (d, J=15.60 Hz, 1H), 6.48 (d, J=8.82 Hz, 1H), 7.20 (m, 4H), 7.52(t, J=7.80 Hz, 1H), 7.59 (m, 1H), 7.68 (s, 1H), 7.71 (d, J=8.48 Hz, 2H),7.79 (d, J=8.48 Hz, 2H), 8.09 (m, 1H), 8.13 (m, 1H), 8.16 (s, 1H)

Example 175

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.87 (m, 1H),2.15 (m, 1H), 2.96 (m, 10H), 3.67 (d, J=10.85 Hz, 1H), 3.78 (dd, J=8.65,5.26 Hz, 1H), 4.17 (dd, J=10.00, 4.58 Hz, 1H), 4.24 (d, J=15.26 Hz, 1H),4.45 (d, J=15.26 Hz, 1H), 6.53 (d, J=8.82 Hz, 1H), 7.17 (m, 5H), 7.30(m, 1H), 7.60 (m, 1H), 7.71 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),8.16 (s, 1H), 8.55 (m, 2H)

Example 176

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.82 (t, J=7.46Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 0.98 (m, 1H),1.29 (m, 1H), 1.92 (m, 2H), 2.99 (m, 9H), 3.75 (m, 2H), 3.80 (s, 3H),3.85 (q, J=5.76 Hz, 1H), 4.06 (m, 1H), 4.63 (d, J=15.26 Hz, 1H), 4.86(d, J=15.26 Hz, 1H), 6.45 (d, J=8.48 Hz, 1H), 7.15 (m, 5H), 7.33 (m,2H), 7.74 (m, 6H), 8.18 (s, 1H)

Example 177

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (t, J=5.76 Hz, 6H), 2.04 (m, 1H),2.54 (m, 2H), 2.71 (m, 3H), 3.14 (m, 5H), 3.28 (s, 3H), 3.49 (m, 5H),3.73 (d, J=10.85 Hz, 1H), 3.79 (m, 1H), 4.07 (m, 1H), 4.42 (d, J=1.70Hz, 2H), 7.12 (m, 5H), 7.21 (s, 1H), 7.77 (d, J=8.48 Hz, 2H), 7.84 (d,J=8.82 Hz, 2H), 7.98 (d, J=9.49 Hz, 1H), 8.14 (d, J=3.39 Hz, 1H)

Example 178

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.44 Hz, 6H), 1.77 (m, 2H),2.00 (m, 2H), 2.55 (m, 3H), 3.12 (m, 7H), 3.40 (m, 4H), 3.46 (s, 3H),3.73 (m, 2H), 4.12 (m, 1H), 4.45 (s, 2H), 4.70 (s, 2H), 7.08 (m, 3H),7.15 (m, 2H), 7.37 (s, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.83 (d, J=8.82 Hz,2H), 7.96 (d, J=9.49 Hz, 1H), 8.14 (s, 1 μl

Example 179

¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (d, J=6.78 Hz, 3H), 0.83 (m, J=7.46Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 0.97 (m, 1H),1.35 (m, 1H), 1.86 (d, J=6.78 Hz, 1H), 1.98 (m, 1H), 2.89 (m, 4H), 3.12(m, 4H), 3.74 (d, J=10.85 Hz, 1H), 3.83 (m, 2H), 4.20 (m, 3H), 4.48 (d,J=15.26 Hz, 1H), 6.53 (d, J=8.48 Hz, 1H), 7.19 (m, 7H), 7.37 (m, 1H),7.67 (d, J=7.80 Hz, 1H), 7.71 (d, J=8.82 Hz, 2H), 7.79 (d, J=8.48 Hz,2H), 8.16 (s, 1H)

Example 180

¹H NMR (300 MHz, CDCl₃) δ ppm 0.70 (d, J=6.44 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 1.02 (s, 1H), 1.36 (m, 1H), 1.65 (dd, J=11.02, 7.97 Hz, 4H),1.85 (m, 2H), 1.98 (m, 4H), 2.52 (m, 1H), 2.80 (dd, J=14.24, 10.17 Hz,1H), 2.91 (s, 1H), 3.16 (m, 5H), 3.72 (d, J=10.85 Hz, 1H), 3.79 (m, 1H),4.20 (m, J=15.26 Hz, 2H), 4.52 (d, J=15.60 Hz, 1H), 6.65 (s, 1H), 7.20(m, 7H), 7.45 (s, 1H), 7.71 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 3H),8.16 (s, 1H)

Example 181

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.87 (m, 9H),1.01 (d, J=22.72 Hz, 1H), 1.37 (m, 1H), 1.87 (d, J=6.78 Hz, 2H), 2.00(m, 1H), 2.96 (m, 9H), 3.79 (m, J=10.85 Hz, 2H), 4.27 (m, J=15.94 Hz,2H), 4.49 (d, J=15.94 Hz, 1H), 6.53 (d, J=8.82 Hz, 1H), 7.20 (m, 5H),7.30 (s, 2H), 7.69 (d, J=8.48 Hz, 2H), 7.80 (d, J=8.14 Hz, 2H), 8.16 (s,1H), 8.60 (s, 2H)

Example 182

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.87 (t, J=7.29Hz, 3H), 1.03 (s, 1H), 1.43 (s, 1H), 1.69 (m, 2H), 1.86 (m, 2H), 1.98(m, 4H), 2.50 (m, 1H), 2.82 (m, 1H), 3.13 (m, 8H), 3.82 (m, J=10.51 Hz,2H), 4.28 (m, J=16.62 Hz, 2H), 4.51 (d, J=16.28 Hz, 1H), 6.59 (d, J=8.82Hz, 1H), 7.21 (m, J=13.05, 4.24 Hz, 5H), 7.34 (s, 2H), 7.68 (d, J=8.48Hz, 2H), 7.80 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.61 (s, 2H)

Example 183

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (m, 6H), 1.16 (t, J=6.44 Hz, 3H),2.01 (m, 1H), 2.52 (m, 2H), 2.70 (s, 3H), 2.91 (m, 1H), 3.13 (m, 9H),3.63 (m, 1H), 3.72 (m, 1H), 3.89 (m, 1H), 4.06 (m, 1H), 4.42 (d, J=2.03Hz, 2H), 7.08 (m, 3H), 7.14 (m, 2H), 7.21 (s, 1H), 7.78 (d, J=8.82 Hz,2H), 7.83 (d, J=8.82 Hz, 2H), 8.14 (s, 1H)

Example 184

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 1.00 (m, 2H), 1.35 (m, 2H), 1.66 (m, 4H), 1.82 (m, 1H), 1.98(m, 4H), 2.48 (dd, J=15.26, 7.46 Hz, 1H), 2.81 (m, 2H), 3.11 (m, 3H),3.79 (m, 2H), 3.86 (m, 1H), 4.24 (m, 1H), 4.80 (t, J=15.60 Hz, 2H), 6.60(d, J=8.82 Hz, 1H), 7.16 (m, 5H), 7.27 (m, 1H), 7.60 (m, 1H), 7.72 (m,4H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.17 (m, 2H)

Example 185

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.78 Hz, 6H), 2.07 (m, 1H),2.55 (m, 2H), 2.70 (s, 3H), 3.14 (m, 6H), 3.43 (m, 2H), 3.58 (m, 2H),3.77 (m, 2H), 4.10 (m, 1H), 4.42 (d, J=1.36 Hz, 2H), 6.82 (d, J=2.37 Hz,1H), 6.90 (dd, J=509, 3.39 Hz, 1H), 7.09 (m, 3H), 7.18 (m, 3H), 7.20 (s,1H), 7.77 (d, J=8.82 Hz, 2H), 7.82 (d, J=8.82 Hz, 2H), 8.02 (d, J=9.83Hz, 1H), 8.14 (s, 1H)

Example 186

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.61 (d, J=6.44 Hz, 3H), 0.76 (d, J=7.46Hz, 3H), 0.81 (d, J=6.78 Hz, 6H), 0.92 (m, 2H), 1.06 (m, 1H), 1.26 (m,1H), 1.76 (s, 1H), 1.98 (d, J=6.78 Hz, 1H), 2.40 (dd, J=13.56, 11.19 Hz,1H), 2.59 (m, 2H), 2.63 (s, 3H), 2.98 (m, 2H), 3.13 (d, J=7.80 Hz, 1H),3.25 (d, J=17.29 Hz, 2H), 3.58 (d, J=7.46 Hz, 1H), 3.85 (m, J=10.85 Hz,2H), 4.31 (d, J=8.48 Hz, 2H), 4.95 (d, J=6.44 Hz, 1H), 7.06 (m, 5H),7.22 (s, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H), 8.24 (s,1H)

Example 187

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J=6.78 Hz, 3H), 0.78 (t, J=7.12Hz, 3H), 0.92 (m, 2H), 1.24 (s, 1H), 1.60 (m, J=29.84, 8.82 Hz, 2H),1.73 (m, 4H), 1.89 (m, 2H), 2.42 (dd, J=13.73, 11.02 Hz, 1H), 2.59 (m,2H), 2.64 (s, 3H), 3.09 (m, 6H), 3.56 (d, J=3.73 Hz, 1H), 3.86 (d,J=10.85 Hz, 2H), 4.32 (m, 2H), 4.99 (d, J=6.44 Hz, 1H), 7.06 (m, 3H),7.22 (s, 1H), 7.79 (m, 4H), 7.91 (m, 2H), 8.24 (s, 1H)

Example 188

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.85 (t, J=6.78Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 0.94 (m, 1H), 1.37 (m, 1H), 1.85 (m,1H), 2.04 (s, 1H), 2.83 (m, 4H), 3.06 (m, 6H), 3.83 (m, 2H), 4.23 (s,1H), 4.81 (m, J=13.90 Hz, 2H), 6.53 (d, J=8.48 Hz, 1H), 7.16 (m, 5H),7.61 (t, J=7.46 Hz, 1H), 7.74 (m, 5H), 8.15 (m, 3H), 8.24 (m, 2H)

Example 189

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=6.78 Hz, 3H), 0.79 (m, 3H),0.88 (m, 1H), 1.19 (m, 1H), 1.60 (m, 1H), 1.73 (m, 4H), 1.87 (dd,J=13.22, 7.80 Hz, 2H), 2.12 (s, 3H), 2.43 (dd, J=13.56, 10.85 Hz, 1H),2.57 (m, 1H), 2.67 (m, J=7.12 Hz, 1H), 3.09 (m, 8H), 3.56 (s, 1H), 3.85(m, J=10.85 Hz, 2H), 4.26 (t, J=15.26 Hz, 2H), 4.99 (d, J=6.10 Hz, 1H),6.88 (s, 1H), 7.07 (m, 5H), 7.79 (m, 4H), 7.87 (d, J=9.49 Hz, 1H), 8.24(s, 1H)

Example 190

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62 (d, J=6.78 Hz, 3H), 0.80 (m, 9H),0.89 (m, 1H), 1.22 (m, 1H), 1.72 (d, J=2.37 Hz, 1H), 1.99 (m, 1H), 2.12(s, 3H), 2.41 (dd, J=13.39, 11.02 Hz, 1H), 2.67 (m, 1H), 2.87 (dd,J=13.73, 6.61 Hz, 1H), 3.10 (m, 6H), 3.58 (d, J=6.10 Hz, 1H), 3.85 (m,2H), 4.26 (t, J=15.26 Hz, 2H), 4.95 (d, J=6.44 Hz, 1H), 6.88 (s, 1H),7.06 (m, 5H), 7.78 (m, 4H), 7.88 (d, J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 191

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.44 Hz, 3H), 0.86 (m, 6H),0.91 (d, J=6.78 Hz, 3H), 0.99 (m, 1H), 1.32 (m, 1H), 1.85 (m, 1H), 2.02(m, 1H), 2.48 (m, 2H), 3.07 (m, 8H), 3.44 (dd, J=14.92, 3.39 Hz, 1H),3.75 (m, 1H), 3.85 (d, J=11.19 Hz, 1H), 4.10 (m, 1H), 4.41 (d, J=14.58Hz, 1H), 4.57 (d, J=14.92 Hz, 1H), 6.98 (dd, J=4.92, 1.87 Hz, 3H), 7.13(m, 2H), 7.25 (m, 1H), 7.59 (m, 2H), 7.78 (d, J=8.48 Hz, 2H), 7.84 (d,J=8.82 Hz, 2H), 8.14 (s, 1 H), 8.16 (s, 1H)

Example 192

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (m, 9H), 0.95 (d, J=6.78 Hz, 3H),2.04 (m, 2H), 2.52 (m, 1H), 2.69 (d, J=4.07 Hz, 3H), 3.16 (m, 7H), 3.46(m, 3H), 3.73 (m, 3H), 3.83 (m, 1H), 4.09 (s, 1H), 4.42 (s, 2H), 7.11(m, 5H), 7.22 (m, 1H), 7.75 (d, J=8.48 Hz, 2H), 7.89 (d, J=8.48 Hz, 2H),8.14 (s, 1H)

Example 193

¹H NMR (300 MHz, CD₃OD) δ ppm 0.65 (dd, J=9.16, 6.78 Hz, 3H), 0.82(0=6.95 Hz, 6H), 0.95 (d, J=6.44 Hz, 3H), 1.89 (m, 1H), 2.06 (m, 1H),2.50 (dd, J=13.73, 10.68 Hz, 1H), 2.64 (m, 1H), 2.70 (s, 3H), 3.10 (m,6H), 3.54 (m, 1H), 3.65 (m, 2H), 3.76 (m, 2H), 4.00 (m, 2 H), 4.43 (s,2H), 7.17 (m, 6H), 7.73 (m, 3H), 7.87 (m, 1H), 8.06 (m, 1H), 8.14 (s,1H)

Example 194

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=6.78 Hz, 3H), 0.80 (m, 3H),0.92 (m, 1H), 1.20 (m, 4H), 1.53 (m, 6H), 1.77 (d, J=3.05 Hz, 1H), 2.25(m, J=7.46 Hz, 1H), 2.40 (dd, J=13.39, 11.02 Hz, 1H), 3.09 (m, 8H), 3.60(s, 1H), 3.91 (m, J=10.85 Hz, 2H), 4.80 (d, J=3.05 Hz, 2H), 4.96 (d,J=6.44 Hz, 1H), 6.93 (m, 3H), 7.05 (d, J=6.44 Hz, 2H), 7.42 (d, J=4.41Hz, 1H), 7.62 (t, J=7.12 Hz, 1H), 7.79 (m, 4H), 7.97 (d, J=9.49 Hz, 1H),8.06 (d, J=7.80 Hz, 1H), 8.24 (s, 1H), 8.30 (d, J=7.80 Hz, 1H), 8.89 (d,J=4.41 Hz, 1H)

Example 195

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.84 (dd,J=12.72, 6.95 Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 1.00 (m, 1H), 1.33 (s,1H), 1.87 (d, J=6.78 Hz, 1H), 1.99 (s, 1H), 2.34 (s, 3H), 2.75 (dd,J=14.24, 9.83 Hz, 1H), 2.88 (m, 3H), 3.09 (m, 6H), 3.76 (d, J=10.85 Hz,1H), 3.81 (s, 1H), 4.17 (m, 1H), 4.28 (d, J=14.92 Hz, 1H), 4.44 (d,J=14.92 Hz, 1H), 6.49 (d, J=8.82 Hz, 1H), 7.19 (m, 6H), 7.71 (d, J=8.48Hz, 2H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.42 (m, 2H)

Example 196

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.85 (m, 6H),0.91 (d, J=6.44 Hz, 3H), 1.03 (m, 1H), 1.35 (d, J=3.05 Hz, 1H), 1.86 (m,1H), 1.96 (s, 1H), 2.56 (s, 3H), 2.74 (dd, J=14.24, 10.17 Hz, 1H), 3.02(m, 8H), 3.80 (m, 2H), 3.88 (d, J=3.39 Hz, 1H), 4.12 (m, 1H), 4.38 (d,J=15.60 Hz, 1H), 4.59 (d, J=15.60 Hz, 1H), 6.49 (d, J=8.82 Hz, 1H), 7.06(d, J=7.46 Hz, 2H), 7.18 (m, 5H), 7.58 (m, 1H), 7.70 (d, J=8.48 Hz, 2H),7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 197

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.89 (m, 9H),1.01 (s, 1H), 1.39 (s, 1H), 1.87 (m, 1H), 1.97 (s, 1H), 2.75 (dd,J=14.24, 10.17 Hz, 1H), 3.03 (m, 8H), 3.77 (d, J=10.85 Hz, 1H), 3.79 (s,1H), 3.90 (d, J=3.05 Hz, 1H), 4.16 (s, 1H), 4.40 (d, J=15.60 Hz, 1H),4.59 (d, J=15.60 Hz, 1H), 6.53 (d, J=8.82 Hz, 1H), 7.18 (m, 7H), 7.70(m, J=8.48 Hz, 3H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.56 (d,J=4.07 Hz, 1H)

Example 198

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.85 (t, J=7.29Hz, 6H), 0.91 (d, J=6.78 Hz, 3H), 1.01 (m, 1H), 1.39 (m, 1H), 1.88 (m,1H), 1.98 (m, 1H), 2.75 (dd, J=14.41, 10.00 Hz, 1H), 2.87 (dd, J=13.73,6.95 Hz, 2H), 2.99 (m, 1H), 3.17 (m, 4H), 3.48 (s, 3H), 3.81 (m, 3H),4.17 (m, 1H), 4.37 (d, J=15.60 Hz, 1H), 4.56 (s, 2H), 4.60 (d, J=15.94Hz, 1H), 6.50 (d, J=8.48 Hz, 1H), 7.17 (m, 5H), 7.32 (d, J=7.80 Hz, 1H),7.68 (m, 4H), 7.79 (d, J=8.82 Hz, 2H), 8.15 (s, 1H), 8.17 (s, 1H)

Example 199

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.83 (t, J=7.12Hz, 3H), 0.98 (m, 1H), 1.39 (m, 2H), 1.55 (m, 6H), 1.96 (s, 2H), 2.13(m, 2H), 2.78 (m, 2H), 3.11 (m, 7H), 3.47 (s, 3H), 3.80 (d, J=10.85 Hz,1H), 3.86 (m, 1H), 4.20 (m, 1H), 4.37 (d, J=15.94 Hz, 1H), 4.56 (s, 2H),4.61 (d, J=15.60 Hz, 1H), 6.66 (d, J=9.16 Hz, 1H), 7.17 (m, 6H), 7.33(d, J=7.80 Hz, 1H), 7.68 (m, 3H), 7.79 (d, J=8.48 Hz, 2H), 8.15 (s, 1H)

Example 200

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.88 (m, J=6.95,2.20 Hz, 6H), 0.91 (d, J=6.44 Hz, 3H), 1.03 (m, 1H), 1.41 (m, 1H), 1.89(m, 1H), 2.02 (m, 1H), 2.51 (dd, J=13.73, 11.36 Hz, 1H), 2.64 (m, 1H),3.10 (m, 8H), 3.45 (dd, J=14.92, 3.39 Hz, 1H), 3.76 (m, 1H), 3.87 (d,J=11.19 Hz, 1H), 4.14 (m, 1H), 4.53 (d, J=15.94 Hz, 1H), 4.78 (d,J=10.17 Hz, 1H), 7.09 (m, 3H), 7.18 (m, 2H), 7.47 (d, J=8.48 Hz, 1H),7.60 (m, 1H), 7.76 (m, 3H), 7.84 (d, J=8.48 Hz, 2H), 7.92 (m, 1H), 8.02(m, 1H), 8.14 (s, 1H), 8.34 (d J=8.48 Hz, 1H)

Example 201

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.87 (m, 6H),0.91 (d, J=6.44 Hz, 3H), 1.00 (m, 1H), 1.30 (m, 1H), 1.86 (m, 1H), 2.02(m, 1H), 2.49 (m, 1H), 2.58 (m, 1H), 3.07 (m, 6H), 3.45 (dd, J=14.92,3.39 Hz, 1H), 3.75 (m, 1H), 3.84 (d, J=11.19 Hz, 1H), 4.13 (m, 1H), 4.31(d, J=15.26 Hz, 1H), 4.52 (d, J=15.60 Hz, 1H), 7.07 (m, 3H), 7.17 (m,2H), 7.59 (m, 2H), 7.67 (m, 1H), 7.78 (d, J=8.48 Hz, 2H), 7.84 (d,J=8.82 Hz, 2H), 7.98 (s, 1H), 8.14 (s, 1H)

Example 202

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.61 (d, J=6.78 Hz, 3H), 0.78 (dd,J=16.95, 7.12 Hz, 9H), 0.91 (m, 1H), 1.26 (m, 1H), 1.73 (s, 1H), 1.98(m, J=6.44 Hz, 1H), 2.39 (dd, J=13.22, 11.19 Hz, 1H), 2.58 (t, J=7.97Hz, 1H), 3.05 (m, 9H), 3.58 (m, 1H), 3.84 (m, J=10.85 Hz, 2H), 4.49 (m,2H), 7.05 (m, 5H), 7.76 (d, J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H),7.94 (s, 1H), 8.24 (s, 1H)

Example 203

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.82 (t, J=7.29Hz, 3H), 0.95 (m, 1H), 1.24 (m, 5H), 1.53 (m, 4H), 1.96 (m, 1H), 2.15(m, 1H), 2.99 (m, 12H), 3.76 (d, J=11.19 Hz, 1H), 3.88 (m, 1H), 3.96 (d,J=2.71 Hz, 1H), 4.11 (m, 1H), 4.62 (d, J=14.92 Hz, 1H), 4.86 (d, J=15.26Hz, 1H), 6.45 (d, J=8.82 Hz, 1H), 7.15 (m, 5H), 7.33 (m, 2H), 7.74 (m,6H), 8.18 (s, 1H)

Example 204

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.84 (t, J=7.29Hz, 3H), 0.98 (m, 2H), 1.21 (m, 2H), 1.38 (m, 2H), 1.64 (m, 6H), 1.97(s, 1H), 2.10 (m, 1H), 2.74 (m, 3H), 3.09 (m, 5H), 3.81 (m, 2H), 4.13(m, 1H), 5.10 (d, J=2.03 Hz, 2H), 6.58 (d, J=8.82 Hz, 1H), 7.13 (m, 5H),7.44 (dd, J=8.31, 4.24 Hz, 1H), 7.52 (m, 1H), 7.69 (m, 3H), 7.77 (m,3H), 8.15 (s, 1H), 8.18 (dd, J=8.31, 1.53 Hz, 1H), 8.95 (d, J=2.37 Hz,1H)

Example 205

¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (s, 3H), 0.87 (s, 9H), 1.01 (s, 1H),1.40 (s, 1H), 1.90 (m, 2H), 2.98 (s, 11H), 3.82 (m, 3H), 4.17 (s, 1H),5.09 (m, 2H), 7.14 (m, 5H), 7.45 (dd, J=8.14, 4.07 Hz, 1H), 7.52 (m,1H), 7.69 (m, 3H), 7.78 (m, 3H), 8.18 (d, J=8.14 Hz, 1H), 8.96 (d,J=2.37 Hz, 1H)

Example 206

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.79 (m, J=15.77, 6.95 Hz, 6H), 1.23(dd, J=14.07, 6.27 Hz, 6H), 1.32 (d, J=7.12 Hz, 6H), 1.75 (s, 1H), 1.96(d, J=7.80 Hz, 1H), 2.39 (dd, J=13.39, 11.02 Hz, 1H), 3.07 (m, 11H),3.61 (m, 1H), 3.84 (m, J=10.85 Hz, 2H), 4.36 (m, 2H), 4.95 (d, J=6.44Hz, 1H), 7.05 (m, 5H), 7.24 (s, 1H), 7.78 (t, J=8.82 Hz, 4H), 7.89 (d,J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 207

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.63 (d, J=6.44 Hz, 3H), 0.77 (t,J=7.12 Hz, 3H), 0.90 (m, 1H), 1.23 (dd, J=14.07, 6.61 Hz, 4H), 1.32 (d,J=6.78 Hz, 6H), 1.52 (m, 6H), 1.71 (d, J=16.28 Hz, 1H), 2.26 (m, 1H),2.40 (dd, J=13.22, 10.85 Hz, 1H), 2.57 (m, 1H), 3.11 (m, 7H), 3.59 (d,J=12.55 Hz, 1H), 3.85 (m, J=11.19 Hz, 2H), 4.30 (d, J=15.60 Hz, 1H),4.39 (d, J=15.26 Hz, 1H), 4.95 (d, J=6.44 Hz, 1H), 7.05 (m, 5H), 7.25(s, 1H), 7.78 (t, J=8.82 Hz, 4H), 7.89 (d, J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 208

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.66 (d, J=6.44 Hz, 3H), 0.70 (d, J=6.44Hz, 3H), 0.81 (d, J=6.78 Hz, 6H), 1.23 (dd, J=13.73, 5.93 Hz, 6H), 1.32(d, J=7.12 Hz, 6H), 1.94 (m, 1H), 2.40 (dd, J=13.22, 11.19 Hz, 1H), 3.00(m, 2H), 3.21 (m, 2H), 3.59 (s, 1H), 3.75 (d, J=10.85 Hz, 1H), 3.85 (s,1H), 4.30 (d, J=15.26 Hz, 1H), 4.39 (d, J=15.26 Hz, 1H), 4.96 (d, J=6.78Hz, 1H), 7.05 (m, 5H), 7.24 (s, 1H), 7.78 (t, J=8.82 Hz, 4H), 7.89 (d,J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 209

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.69 (t, J=7.12 Hz, 6H), 0.85 (m, 1H),1.19 (m, 4H), 1.32 (d, J=6.78 Hz, 6H), 1.53 (m, 6H), 1.94 (m, 1H), 2.22(m, 1H), 2.40 (dd, J=13.39, 11.02 Hz, 1H), 3.11 (m, 6H), 3.61 (m, 1H),3.76 (d, J=10.85 Hz, 1H), 3.88 (s, 1H), 4.35 (dd, J=15.60, 14.92 Hz,2H), 4.96 (d, J=6.44 Hz, 1H), 7.06 (m, 5H), 7.24 (s, 1H), 7.78 (dd,J=9.16, 8.48 Hz, 4H), 7.88 (d, J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 210

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.61 (d, J=6.44 Hz, 3H), 0.76 (d,J=7.12 Hz, 3H), 0.81 (d, J=6.78 Hz, 3H), 1.26 (d, J=5.76 Hz, 3H), 1.73(s, 1H), 1.97 (s, 1H), 2.40 (dd, J=13.39, 10.68 Hz, 1H), 2.60 (d, J=7.46Hz, 1H), 2.89 (m, 1H), 2.99 (m, 3H), 3.01 (m, 4H), 3.13 (d, J=8.14 Hz,1H), 3.23 (m, 1H), 3.38 (s, 3H), 3.61 (m, J=10.85 Hz, 1H), 3.85 (m,J=11.19 Hz, 2H), 4.37 (s, 1H), 4.67 (d, J=4.07 Hz, 2H), 4.95 (d, J=6.44Hz, 1H), 7.05 (m, 5H), 7.41 (s, 1H), 7.78 (t, J=12.21 Hz, 4H), 7.90 (d,J=9.83 Hz, 1H), 8.24 (s, 1H)

Example 211

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J=6.44 Hz, 3H), 0.77 (t, J=7.29Hz, 3H), 0.89 (m, 1H), 1.24 (m, 7H), 1.56 (d, J=7.80 Hz, 6H), 1.72 (d,J=23.06 Hz, 1H), 2.22 (s, 1H), 2.42 (m, 1H), 2.60 (d, J=7.12 Hz, 1H),2.99 (m, 1H), 3.13 (m, 1H), 3.38 (s, 3H), 3.61 (m, 2H), 3.85 (m, J=11.19Hz, 2H), 4.37 (s, 2H), 4.68 (s, 2H), 4.95 (d, J=6.44 Hz, 1H), 7.07 (m,5H), 7.41 (s, 1H), 7.78 (m, 4H), 7.90 (d, J=9.16 Hz, 1H), 8.24 (s, 1H)

Example 212

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 12H), 1.03 (m, J=15.94 Hz, 1H),1.43 (m, 1H), 1.85 (m, 1H), 1.99 (m, 1H), 2.35 (s, 3H), 2.87 (m, 4H),3.12 (m, 7H), 3.78 (d, J=11.19 Hz, 1H), 3.95 (m, 1H), 4.20 (m, J=15.94Hz, 2H), 4.51 (d, J=15.94 Hz, 1H), 6.63 (d, J=7.46 Hz, 1H), 7.14 (m,5H), 7.71 (m, 3H), 7.80 (m, 3H), 8.15 (s, 1H), 8.55 (d, J=5.09 Hz, 1H)

Example 213

¹H NMR (300 MHz, CDCl₃) δ ppm 0.69 (d, J=6.44 Hz, 3H), 0.87 (m, 9H),0.98 (m, 1H), 1.39 (m, 1H), 1.89 (dd, J=13.73, 6.95 Hz, 1H), 2.03 (m,1H), 3.02 (m, 9H), 3.72 (m, 1H), 3.87 (m, 1H), 4.17 (m, 2H), 4.44 (d,J=14.92 Hz, 1H), 4.67 (d, J=15.26 Hz, 1H), 6.83 (d, J=8.82 Hz, 1H), 7.18(m, 5H), 7.45 (m, 2H), 7.79 (m, 5H), 8.10 (s, 1H), 8.18 (s, 1H), 8.19(m, 1H), 8.94 (d, J=2.71 Hz, 1H)

Example 214

¹H NMR (300 MHz, CDCl₃) δ ppm 0.69 (d, J=6.44 Hz, 3H), 0.87 (m, 12H),0.99 (m, 1H), 1.39 (m, 1H), 1.89 (dd, J=13.73, 6.95 Hz, 2H), 2.02 (m,2H), 3.01 (m, 5H), 3.71 (d, J=11.19 Hz, 1H), 3.87 (m, 1H), 4.17 (m, 1H),4.44 (d, J=14.92 Hz, 1H), 4.66 (m, 1H), 6.83 (d, J=8.82 Hz, 1H), 7.18(m, 5H), 7.45 (m, 2H), 7.79 (m, 5H), 810 (s, 1H), 8.20 (m, 1H), 8.18 (s,1H), 8.94 (d, J=2.71 Hz, 1H)

Example 215

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.62 (d, J=6.44 Hz, 3H), 0.77 (d,J=7.46 Hz, 3H), 0.81 (d, J=6.44 Hz, 6H), 0.92 (m, 1H), 1.26 (m, 2H),1.74 (s, 1H), 1.98 (m, J=5.09 Hz, 1H), 2.40 (dd, J=13.39, 11.02 Hz, 1H),2.60 (m, J=8.14 Hz, 1H), 3.06 (m, 8H), 3.58 (m, 1H), 3.87 (d, J=10.85Hz, 2H), 4.47 (m, 2H), 7.01 (m, 5H), 7.49 (dd, J=6.44, 4.75 Hz, 1H),7.57 (s, 1H), 7.78 (m, 4H), 7.94 (m, 2H), 8.09 (m, 1H), 8.24 (s, 1H)

Example 216

¹H NMR (300 MHz, CDCl₃) δ ppm 0.69 (d, J=6.78 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 0.97 (m, 1H), 1.24 (m, 3H), 1.38 (m, 1H), 1.55 (m, 6H), 2.01(m, 1H), 2.15 (m, 1H), 3.03 (m, 7H), 3.72 (m, 1H), 3.90 (m, 1H), 4.19(m, 2H), 4.43 (d, J=14.92 Hz, 1H), 4.67 (d, J=15.26 Hz, 1H), 6.82 (d,J=8.82 Hz, 1H), 7.16 (m, 6H), 7.46 (m, 2H), 7.78 (m, 5H), 8.10 (s, 1H),8.20 (m, 1H), 8.18 (s, 1H), 8.94 (dd, J=4.41, 1.70 Hz, 1H)

Example 217

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.86 (t, J=7.29Hz, 3H), 1.01 (m, 1H), 1.23 (m, 2H), 1.38 (m, 1H), 1.57 (m, 6H), 2.01(m, 1H), 2.11 (dd, J=14.75, 7.29 Hz, 1H), 2.99 (m, 9H), 3.84 (m, 3H),4.24 (m, 1H), 4.41 (d, J=15.26 Hz, 1H), 4.63 (d, J=14.92 Hz, 1H), 6.58(d, J=8.82 Hz, 1H), 7.17 (m, 5H), 7.42 (dd, J=8.31, 4.24 Hz, 1H), 7.62(dd, J=8.48, 2.03 Hz, 1H), 7.69 (m, 3H), 7.79 (d, J=8.82 Hz, 2H), 8.12(dd, J=8.82, 6.78 Hz, 2H), 8.16 (s, 1H), 8.91 (d, J=3.05 Hz, 1H)

Example 218

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.62 (t, J=6.61 Hz, 3H), 0.76 (d,J=7.46 Hz, 3H), 0.81 (d, J=6.78 Hz, 6H), 0.91 (m, 1H), 1.24 (m, 2H),1.73 (0=10.51 Hz, 1H), 1.98 (m, 1H), 2.41 (dd, J=13.22, 11.19 Hz, 1H),2.63 (t, J=7.63 Hz, 1H), 2.87 (dd, J=13.56, 6.44 Hz, 1H), 3.00 (s, 6H),3.14 (m, 6H), 3.56 (m, 1H), 3.85 (d, J=11.19 Hz, 2H), 4.32 (s, 2H), 4.95(d, J=6.44 Hz, 1H), 7.05 (m, 5H), 7.33 (s, 1H), 7.78 (m, 4H), 7.90 (d,J=9.49 Hz, 1H), 8.24 (s, 1H).

Example 219

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 1.00 (s, 9H), 1.37 (m, 1H), 1.89 (s, 1H), 2.56 (dd, J=14.07,11.02 Hz, 1H), 3.15 (m, 7H), 3.39 (m, 2H), 3.48 (m, 1H), 3.81 (d,J=11.19 Hz, 1H), 3.91 (m, 1H), 4.02 (m, 2H), 4.07 (s, 3H), 4.74 (d,J=16.95 Hz, 1H), 5.01 (d, J=16.95 Hz, 1H), 7.13 (m, 5H), 7.66 (m, 2H),7.78 (m, 3H), 7.83 (d, J=8.48 Hz, 2H), 7.89 (m, 1H), 8.14 (s, 1H)

Example 220

¹H NMR (300 MHz, CD₃OD) δ ppm 0.65 (d, J=6.44 Hz, 3H), 0.73 (d, J=6.78Hz, 3H), 0.96 (m, 2H), 1.97 (m, 1H), 2.45 (m, 2H), 2.69 (s, 3H), 3.12(m, 4H), 3.52 (m, 3H), 3.98 (s, 1H), 4.41 (m, 2H), 4.69 (dd, J=36.11,16.11 Hz, 2H), 7.08 (m, 5H), 7.19 (s, 1H), 7.62 (d, J=8.48 Hz, 2H), 7.87(m, 7H), 8.15 (s, 1H), 8.28 (d, J=8.14 Hz, 1H), 8.53 (m, 1H), 8.78 (d,J=4.75 Hz, 1H)

Example 221

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.86 (t, J=7.29Hz, 3H), 1.02 (m, 1H), 1.12 (s, 2H), 1.44 (m, 8H), 2.00 (s, 1H), 2.10(m, 1H), 2.35 (s, 3H), 2.87 (dd, J=14.24, 10.17 Hz, 1H), 3.01 (dd,J=11.19, 7.80 Hz, 2H), 3.12 (m, 5H), 3.26 (m, 1H), 3.79 (d, J=10.85 Hz,1H), 3.99 (s, 1H), 4.18 (m, 2H), 4.51 (d, J=15.94 Hz, 1H), 6.63 (m, 1H),7.10 (dd, J=5.09, 1.70 Hz, 1H), 7.18 (m, 5H), 7.71 (m, J=8.31, 8.31 Hz,3H), 7.79 (d, J=8.48 Hz, 2H), 8.15 (s, 1H), 8.55 (d, J=5.09 Hz, 1H)

Example 222

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.44 Hz, 3H), 0.86 (m, J=12.21,6.78 Hz, 6H), 0.91 (d, J=6.44 Hz, 3H), 1.00 (m, 1H), 1.36 (s, 1H), 1.89(s, 1H), 1.99 (d, J=15.26 Hz, 1H), 2.28 (s, 3H), 2.49 (m, J=13.73, 11.36Hz, 1H), 2.60 (m, J=8.48 Hz, 1H), 3.00 (m, 1H), 3.09 (m, 6H), 3.08 (m,1H), 3.18 (m, 1H), 3.44 (d, J=18.65 Hz, 1H), 3.75 (m, 1H), 3.83 (d,J=11.53 Hz, 1H), 4.12 (m, 1H), 4.37 (d, J=15.60 Hz, 1H), 4.63 (m, 1H),7.12 (m, 5H), 7.26 (d, J=7.80 Hz, 1H), 7.75 (m, 3H), 7.84 (d, J=8.48 Hz,2H), 8.15 (s, 1H)

Example 223

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.86 (dd, J=9.16,7.12 Hz, 6H), 0.91 (d, J=6.44 Hz, 3H), 1.03 (d, J=10.85 Hz, 1H), 1.35(s, 1H), 1.87 (s, 1H), 2.02 (m, 1H), 2.17 (d, J=6.10 Hz, 3H), 2.50 (dd,J=13.73, 11.36 Hz, 1H), 2.63 (m, 1H), 3.07 (m, 8H), 3.11 (s, 3H), 3.44(dd, J=14.92, 3.05 Hz, 1H), 3.75 (dd, J=15.60, 3.73 Hz, 1H), 3.82 (dd,J=11.19, 2.71 Hz, 1H), 4.10 (m, J=6.78 Hz, 1H), 4.35 (d, J=15.94 Hz,1H), 4.58 (d, J=15.60 Hz, 1H), 4.68 (s, 2H), 7.13 (m, 5H), 7.24 (m, 1H),7.80 (m, 5H), 7.95 (d, J=9.83 Hz, 1H), 8.14 (s, 1H)

Example 224

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.85 (m, J=14.75,6.95 Hz, 6H), 0.91 (d, J=6.78 Hz, 3H), 0.96 (m, 1H), 1.34 (m, 1H), 1.86(m, J=17.97 Hz, 1H), 2.01 (m, 1H), 2.49 (m, 2H), 3.08 (m, 9H), 3.28 (s,3H), 3.44 (dd, J=14.58, 3.39 Hz, 1H), 3.73 (m, 1H), 3.81 (d, J=11.19 Hz,1H), 4.10 (m, 1H), 4.21 (d, J=6.10 Hz, 1H), 4.57 (m, 2H), 6.40 (s, 1H),7.13 (m, 5H), 7.78 (d, J=8.48 Hz, 2H), 7.84 (m, J=8.48 Hz, 2H), 8.15 (s,1H)

Example 225

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.62 (d, J=6.44 Hz, 3H), 0.77 (d,J=7.12 Hz, 3H), 0.81 (d, J=6.78 Hz, 6H), 0.89 (m, 1H), 1.28 (m, 1H),1.74 (s, 1H), 1.96 (m, 1H), 2.40 (dd, J=13.39, 11.02 Hz, 1H), 2.61 (m,1H), 3.06 (m, 10H), 3.59 (m, 1H), 3.87 (d, J=10.85 Hz, 1H), 4.48 (s,2H), 7.01 (m, 5H), 7.56 (m, 1H), 7.60 (s, 1H), 7.76 (d, J=9.16 Hz, 2H),7.81 (d, J=8.82 Hz, 2H), 7.92 (d, J=9.49 Hz, 1H), 8.24 (s, 1H), 8.31 (s,1H), 8.33 (m, 1H), 8.67 (dd, J=4.75, 1.70 Hz, 1H), 9.15 (d, J=1.70 Hz,1H)

Example 226

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.84 (m, 6H),0.91 (d, J=6.44 Hz, 3H), 0.99 (m, 1H), 1.39 (m, 1H), 1.90 (m, 1H), 2.03(m, 1H), 2.49 (dd, J=13.73, 11.36 Hz, 1H), 2.62 (m, 1H), 3.11 (m, 8H),3.44 (dd, J=14.92, 3.39 Hz, 1H), 3.75 (m, 1H), 3.85 (d, J=11.19 Hz, 1H),4.13 (m, 1H), 4.46 (d, J=15.94 Hz, 1H), 4.71 (d, J=15.94 Hz, 1H), 7.09(m, 5H), 7.37 (d, J=6.78 Hz, 1H), 7.43 (m, 1H), 7.78 (d, J=8.82 Hz, 2H),7.84 (d, J=6.78 Hz, 2H), 7.92 (m, 2H), 8.14 (s, 1H), 8.23 (d, J=7.12 Hz,1H), 8.41 (d, J=8.14 Hz, 1H), 8.63 (m, 1 H)

Example 227

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.85 (dd, J=8.99,6.95 Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 1.01 (m, 1H), 1.33 (m, 1H), 1.85(m, 1H), 1.99 (m, 1H), 2.75 (s, 3H), 2.99 (m, 9H), 3.83 (m, 3H), 4.22(dd, J=9.49, 4.75 Hz, 1H), 4.68 (d, J=15.60 Hz, 1H), 4.82 (d, J=15.26Hz, 1H), 6.54 (d, J=8.82 Hz, 1H), 7.17 (m, 5H), 7.51 (t, J=7.63 Hz, 1H),7.69 (m, 4H), 7.79 (d, J=8.48 Hz, 2H), 8.08 (d, J=8.48 Hz, 2H), 8.16 (s,1H)

Example 228

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.86 (dd, J=7.12,3.39 Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 1.03 (m, 1H), 1.41 (m, 1H), 1.87(m, 1H), 1.99 (m, 1H), 2.67 (s, 3H), 2.76 (m, 1H), 2.88 (m, 1H), 2.99(m, 1H), 3.15 (m, 5H), 3.81 (m, 3H), 3.89 (d, J=3.39 Hz, 1H), 4.16 (m,1H), 4.51 (d, J=15.26 Hz, 1H), 4.78 (d, J=15.26 Hz, 1H), 6.56 (d, J=8.82Hz, 1H), 7.17 (m, 6H), 7.56 (t, J=7.12 Hz, 1H), 7.72 (m, 3H), 7.79 (d,J=8.48 Hz, 2H), 7.98 (d, J=7.46 Hz, 1H), 8.07 (d, J=8.48 Hz, 1H), 8.17(s, 1H)

Example 229

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.88 (m, 9H),1.29 (m, 6H), 1.87 (s, 2H), 2.97 (m, 12H), 3.75 (d, J=11.53 Hz, 2H),3.86 (d, J=3.39 Hz, 1H), 4.12 (q, J=7.12 Hz, 1H), 4.39 (s, 1H), 4.58 (s,1H), 6.50 (d, J=8.82 Hz, 1H), 7.08 (s, 2H), 7.19 (s, 5H), 7.69 (m,J=7.80 Hz, 3H), 7.78 (d, J=8.48 Hz, 2H), 8.15 (s, 1H)

Example 230

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.86 (m, 3H),1.00 (m, 1H), 1.16 (m, 2H), 1.26 (m, J=7.29, 7.29 Hz, 1H), 1.39 (m, 2H),1.64 (m, 6H), 1.97 (m, J=11.53 Hz, 1H), 2.13 (m, 1H), 2.55 (s, 3H), 2.79(m, 2H), 3.10 (m, 5H), 3.79 (m, 3H), 4.15 (m, 1H), 4.40 (m, 1H), 4.59(d, J=15.60 Hz, 1H), 6.52 (d, J=8.82 Hz, 1H), 7.06 (d, J=7.12 Hz, 2H),7.16 (m, 1H), 7.21 (m, 4H), 7.58 (m, 1H), 7.70 (d, J=8.48 Hz, 2H), 7.79(d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 231

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.84 (t, J=7.46Hz, 3H), 0.99 (m, 1H), 1.15 (s, 1H), 1.34 (m, 2H), 1.59 (m, 6H), 1.96(m, 1H), 2.11 (m, J=7.80 Hz, 1H), 2.34 (s, 3H), 2.80 (m, 3H), 3.04 (m,7H), 3.79 (m, 2H), 4.22 (m, 1H), 4.28 (d, J=15.26 Hz, 1H), 4.44 (d,J=14.92 Hz, 1H), 6.51 (d, J=8.82 Hz, 1H), 7.17 (m, 6H), 7.71 (d, J=8.48Hz, 2H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.41 (m, 2H)

Example 232

¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (d, J=6.62 Hz, 3H), 0.85 (m, 6H),0.90 (d, J=6.25 Hz, 3H), 1.00 (m, 1H), 1.85 (m, 1H), 1.95 (m, 1H), 2.99(m, 11H), 3.40 (s, 3H), 3.76 (d, J=11.03 Hz, 1H), 3.82 (m, 1H), 4.16 (m,1H), 4.38 (d, J=15.44 Hz, 1H), 4.44 (s, 2H), 4.58 (d, J=15.44 Hz, 1H),6.62 (d, J=8.82 Hz, 1H), 7.17 (m, 7H), 7.70 (d, J=8.46 Hz, 2H), 7.80 (d,J=8.46 Hz, 2H), 8.15 (s, 1H), 8.50 (d, J=5.15 Hz, 1H)

Example 233

¹H NMR (300 MHz, CD₃OD) δ ppm 0.87 (m, 6H), 0.91 (s, 9H), 1.29 (d,J=2.94 Hz, 1H), 2.02 (m, 1H), 2.26 (m, 1H), 2.43 (dd, J=13.79, 11.58 Hz,1H), 3.06 (m, 8H), 3.43 (dd, J=14.71, 3.31 Hz, 1H), 3.74 (m, 1H), 4.07(m, 1H), 4.58 (s, 2H), 7.10 (m, 5H), 7.58 (s, 1H), 7.78 (m, 5H), 7.96(m, 1H), 8.14 (s, 1H), 8.60 (m, 1H), 8.68 (m, 1H)

Example 234

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.62Hz, 3H), 0.98 (s, 9H), 1.82 (m, 2H), 2.54 (q, J=9.19 Hz, 1H), 2.67 (dd,J=14.34, 10.30 Hz, 1H), 3.04 (m, 5H), 3.31 (m, 1H), 3.82 (m, 2H), 4.07(s, 1H), 4.24 (m, 1H), 4.81 (s, 2H), 6.26 (d, J=8.82 Hz, 1H), 7.04 (m,5H), 7.28 (d, J=4.41 Hz, 1H), 7.61 (m, 1H), 7.72 (m, 3H), 7.80 (d,J=8.46 Hz, 2H), 8.17 (m, 3H), 8.89 (d, J=4.41 Hz, 1H)

Example 235

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.62 Hz, 3H), 0.84 (t, J=7.35Hz, 3H), 0.97 (m, 2H), 1.31 (m, 4H), 1.61 (s, 8H), 1.96 (s, 1H), 2.11(dd, J=15.08, 7.35 Hz, 1H), 2.79 (m, 1H), 3.06 (m, 5H), 3.79 (m, 2H),4.22 (m, 2H), 4.45 (d, J=15.08 Hz, 1H), 6.50 (d, J=8.82 Hz, 1H), 7.17(m, 5H), 7.29 (m, 1H), 7.60 (m, 1H), 7.71 (d, J=8.46 Hz, 2H), 7.79 (d,J=8.82 Hz, 2H), 8.16 (s, 1H), 8.54 (m, 2H)

Example 236

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.92 (d, J=6.62Hz, 3H), 0.96 (s, 9H), 1.87 (m, 1H), 2.59 (q, J=8.95 Hz, 1H), 2.70 (dd,J=14.16, 10.48 Hz, 1H), 3.01 (m, 6H), 3.32 (m, 1H), 3.79 (m, 1H), 4.00(s, 1H), 4.23 (m, 2H), 4.46 (d, J=15.08 Hz, 1H), 6.24 (d, J=9.19 Hz,1H), 7.13 (m, 5H), 7.30 (dd, J=7.35, 4.41 Hz, 1H), 7.62 (m, 1H), 7.72(d, J=8.46 Hz, 2H), 7.80 (d, J=8.46 Hz, 3H), 8.17 (s, 1H), 8.55 (m, 2H)

Example 237

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.61 (d, J=6.62 Hz, 3H), 0.76 (d,J=7.35 Hz, 3H), 0.81 (d, J=6.62 Hz, 6H), 0.91 (m, 1H), 1.22 (m, 1H),1.73 (s, 1H), 1.96 (dd, J=13.42, 6.07 Hz, 1H), 2.04 (s, 2H), 2.07 (s,1H), 2.40 (dd, J=13.24, 11.03 Hz, 1H), 2.61 (m, J=7.35 Hz, 1H), 2.92 (m,6H), 3.03 (s, 3H), 3.15 (m, 1H), 3.24 (m, 1H), 3.58 (m, 1H), 3.84 (d,J=11.03 Hz, 1H), 4.02 (m, 1H), 4.37 (m, 2H), 4.71 (s, 1H), 4.83 (s, 1H),7.06 (m, 5H), 7.35 (m, 1H), 7.79 (t, J=8.82 Hz, 4H), 7.90 (d, J=9.19 Hz,1H), 8.24 (s, 1H)

Example 238

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.62Hz, 3H), 0.98 (s, 9H), 1.86 (m, 1H), 2.53 (m, 1H), 2.67 (dd, J=14.34,10.30 Hz, 1H), 2.75 (s, 3H), 3.07 (m, 7H), 3.81 (m, 2H), 4.07 (s, 1H),4.24 (m, 1H), 4.74 (d, J=16.18 Hz, 2H), 6.23 (d, J=8.82 Hz, 1H), 7.05(m, 5H), 7.18 (s, 1H), 7.52 (t, J=7.72 Hz, 1H), 7.71 (m, 3H), 7.80 (d,J=8.46 Hz, 2H), 8.09 (t, J=9.38 Hz, 2H), 8.17 (s, 1H)

Example 239

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.62Hz, 3H), 0.98 (s, 9H), 1.87 (m, 1H), 2.67 (m, 2H), 3.01 (m, 5H), 3.34(m, 1H), 3.83 (m, 2H), 4.06 (s, 2H), 4.24 (m, 1H), 4.45 (d, J=15.08 Hz,1H), 4.65 (d, J=15.08 Hz, 1H), 6.31 (d, J=8.82 Hz, 1H), 7.14 (m, 5H),7.42 (dd, J=8.27, 4.23 Hz, 1H), 7.65 (m, 1H), 7.71 (d, J=8.82 Hz, 2H),7.79 (d, J=8.46 Hz, 2H), 8.14 (dd, J=8.64, 3.13 Hz, 2H), 8.18 (s, 1H),8.88 (s, 1H), 8.91 (dd, J=4.23, 1.65 Hz, 1H)

Example 240

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.62Hz, 3H), 0.98 (s, 9H), 1.89 (m, 1H), 2.71 (m, 2H), 3.04 (m, 6H), 3.35(m, 1H), 3.84 (m, 1H), 4.04 (m, J=4.78 Hz, 2H), 4.22 (m, 1H), 4.50 (d,J=15.08 Hz, 1H), 4.65 (d, J=15.08 Hz, 1H), 6.41 (d, J=8.82 Hz, 1H), 7.14(m, 5H), 7.43 (dd, J=8.27, 4.23 Hz, 1H), 7.50 (dd, J=8.46, 1.47 Hz, 1H),7.73 (d, J=8.46 Hz, 2H), 7.80 (d, J=8.46 Hz, 2H), 8.05 (s, 1H), 8.17 (d,J=4.78 Hz, 2H), 8.94 (dd, J=4.41, 1.47 Hz, 1H), 9.03 (s, 1H)

Example 241

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (d, J=6.99 Hz, 6H), 0.92 (s, 9H),2.02 (m, 1H), 2.22 (m, 1H), 2.42 (dd, J=13.60, 11.77 Hz, 1H), 3.12 (m,8H), 3.42 (dd, J=15.08, 3.31 Hz, 1H), 3.73 (m, 1H), 4.00 (s, 1H), 4.05(m, 1H), 4.54 (m, 2H), 7.05 (m, 5H), 7.43 (m, 1H), 7.49 (s, 1H), 7.77(d, J=8.82 Hz, 2H), 7.84 (d, J=8.46 Hz, 2H), 7.90 (m, 1H), 8.14 (s, 1H),8.21 (d, J=8.09 Hz, 1H), 8.57 (m, 1H)

Example 242

¹H NMR (300 MHz, DMSO-d₆), δ ppm 0.61 (d, J=6.62 Hz, 3H), 0.77 (m, 3H),0.81 (d, J=6.62 Hz, 6H), 0.92 (m, 1H), 1.21 (m, 2H), 1.73 (m, 1H), 1.97(m, 1H), 2.08 (s, 3H), 2.40 (dd, J=13.42, 10.85 Hz, 1H), 2.60 (m, 1H),2.94 (m, 4H), 3.13 (m, 1H), 3.25 (dd, J=14.52, 2.76 Hz, 1H), 3.57 (m,2H), 3.86 (m, 2H), 4.38 (s, 2H), 5.32 (s, 2H), 7.05 (m, 5H), 7.47 (s,1H), 7.78 (m, 4H), 7.91 (d, J=9.56 Hz, 1H), 8.24 (s, 1H)

Example 243

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.62 Hz, 3H), 0.92 (d, J=6.62Hz, 3H), 0.97 (s, 9H), 1.53 (s, 1H), 1.84 (m, 1H), 2.61 (q, J=9.19 Hz,1H), 2.71 (dd, J=14.34, 10.30 Hz, 1H), 2.87 (dd, J=13.42, 6.80 Hz, 1H),3.09 (m, 5H), 3.34 (m, 1H), 3.48 (s, 3H), 3.79 (m, 1H), 4.00 (s, 1H),4.16 (m, 1H), 4.39 (d, J=15.81 Hz, 1H), 4.57 (s, 2H), 4.64 (d, J=15.81Hz, 1H), 6.18 (d, J=9.19 Hz, 1H), 7.15 (m, 5H), 7.33 (d, J=7.72 Hz, 1H),7.68 (m, 2H), 7.72 (d, J=6.25 Hz, 2H), 7.80 (d, J=8.46 Hz, 2H), 8.16 (s,1

Example 244

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=7.35 Hz, 3H), 0.91 (d, J=6.62Hz, 3H), 0.95 (s, 9H), 1.86 (m, 1H), 2.58 (q, J=8.95 Hz, 1H), 2.69 (dd,J=13.97, 10.30 Hz, 1H), 2.86 (dd, J=13.42, 6.80 Hz, 1H), 3.01 (m, 1H),3.13 (m, 3H), 3.32 (m, 1H), 3.49 (s, 3H), 3.76 (m, 2H), 3.98 (s, 1H),4.18 (m, 1H), 4.43 (d, J=14.71 Hz, 1H), 4.52 (d, J=15.44 Hz, 1H), 4.70(d, J=2.57 Hz, 2H), 6.19 (d, J=8.82 Hz, 1H), 7.11 (s, 1H), 7.15 (m, 5H),7.71 (d, J=8.46 Hz, 2 H), 7.79 (d, J=8.82 Hz, 2H), 7.93 (s, 1H), 8.16(s, 1H)

Example 245

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.62 Hz, 3H), 0.81 (t, J=7.35Hz, 3H), 0.88 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.25 Hz, 3H), 0.99 (m, 1H),1.30 (m, 1H), 1.85 (t, J=15.08 Hz, 1H), 2.01 (m, J=14.71 Hz, 1H), 2.48(m, 2H), 3.07 (m, 8H), 3.44 (dd, J=14.89, 3.49 Hz, 1H), 3.74 (m, 1H),3.85 (d, J=11.03 Hz, 1H), 4.10 (m, 1H), 4.38 (d, J=15.08 Hz, 1H), 4.56(d, J=15.08 Hz, 1H), 7.02 (m, 3H), 7.12 (m, 2H), 7.38 (d, J=7.35 Hz,1H), 7.52 (m, 2H), 7.61 (m, 2H), 7.78 (d, J=8.82 Hz, 2H), 7.83 (d,J=9.93 Hz, 2H), 8.08 (m, 1H), 8.14 (s, 1H), 8.52 (dd, J=4.96, 1.65 Hz,1H), 8.79 (d, J=3.31 Hz, 1H)

Example 246

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.82 (t, J=2.94 Hz, 15H), 1.23 (m, 1H),1.47 (d, J=7.35 Hz, 3H), 1.88 (s, 3H), 1.97 (m, 1H), 2.17 (q, J=8.95 Hz,1H), 2.33 (m, 1H), 3.05 (m, 6H), 3.53 (t, J=8.27 Hz, 1H), 3.84 (m, 1H),3.96 (s, 1H), 4.30 (d, J=15.44 Hz, 1H), 4.42 (d, J=15.44 Hz, 1H), 4.95(d, J=6.62 Hz, 1H), 5.14 (m, 1H), 7.03 (m, 5H), 7.27 (s, 1H), 7.76 (d,J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H), 7.98 (d, J=9.56 Hz, 1H), 8.23(s, 1H), 8.62 (d, J=7.72 Hz, 1H)

Example 247

¹H NMR (300 MHz, CD₃OD) δ ppm 0.87 (m, 6H), 0.91 (s, 9H), 2.00 (dd,J=14.52, 6.80 Hz, 1H), 2.28 (m, 1H), 2.44 (dd, J=13.42, 11.58 Hz, 1H),2.73 (s, 3H), 3.10 (m, 9H), 3.43 (dd, J=14.89, 3.49 Hz, 1H), 3.73 (m,1H), 4.00 (s, 1H), 4.03 (s, 1H), 4.57 (s, 2H), 7.06 (m, 5H), 7.61 (s,1H), 7.78 (m, 2H), 7.83 (d, J=8.46 Hz, 2H), 7.96 (m, 1H), 8.14 (s, 1H),8.69 (dd, J=8.46, 2.21 Hz, 1H)

Example 248

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (m, 6H), 0.91 (s, 9H), 1.99 (s, 1H),2.28 (d, J=8.46 Hz, 1H), 2.44 (m, 1H), 3.06 (m, 8H), 3.41 (d, J=3.68 Hz,1H), 3.73 (s, 1H), 4.00 (s, 1H), 4.07 (m, 1H), 4.59 (s, 2H), 7.07 (m,5H), 7.72 (s, 1H), 7.77 (d, J=8.46 Hz, 2H), 7.82 (m, 3H), 7.94 (s, 1H),8.14 (s, 1H), 8.21 (m, 1H), 8.74 (m, 1H)

Example 249

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (d, J=6.99 Hz, 6H), 0.91 (s, 9H),2.02 (m, 1H), 2.18 (m, 1H), 2.42 (dd, J=13.42, 11.58 Hz, 1H), 3.11 (m,7H), 3.42 (dd, J=14.71, 3.31 Hz, 1H), 3.72 (m, 1H), 3.98 (s, 1H), 4.05(m, 1H), 4.42 (d, J=14.71 Hz, 1H), 4.53 (m, J=13.24 Hz, 2H), 7.06 (m,6H), 7.31 (s, 1H), 7.54 (d, J=5.15 Hz, 1H), 7.60 (d, J=3.68 Hz, 1H),7.77 (d, J=8.82 Hz, 2H), 7.85 (d, J=8.82 Hz, 2H), 8.14 (s, 1H)

Example 250

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.62 Hz, 3H), 0.85 (t, J=7.35Hz, 6H), 0.90 (d, J=6.62 Hz, 3H), 1.35 (m, 3H), 1.85 (m, 1H), 2.00 (m,1H), 2.55 (s, 3H), 2.99 (m, 9H), 3.79 (m, J=11.03 Hz, 2H), 4.20 (m,J=4.78 Hz, 1H), 4.26 (d, J=15.44 Hz, 1H), 4.42 (d, J=15.08 Hz, 1H), 6.49(d, J=8.82 Hz, 1H), 7.17 (m, 6H), 7.45 (dd, J=7.72, 1.47 Hz, 1H), 7.71(d, J=8.46 Hz, 2H), 7.79 (d, J=8.46 Hz, 2H), 8.16 (s, 1H), 8.43 (dd,J=4.96, 1.65 Hz, 1H)

Example 251

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.62 Hz, 3H), 0.84 (dd,J=15.44, 6.99 Hz, 6H), 0.91 (d, J=6.62 Hz, 3H), 0.99 (m, 1H), 1.27 (m,1H), 1.85 (m, J=7.72 Hz, 2H), 2.55 (s, 3H), 2.96 (m, 10H), 3.76 (m, 2H),4.19 (m, J=15.08 Hz, 2H), 4.41 (d, J=15.08 Hz, 1H), 6.45 (d, J=8.82 Hz,1H), 7.18 (m, 5H), 7.49 (dd, J=7.91, 2.39 Hz, 1H), 7.72 (d, J=8.82 Hz,2H), 7.80 (d, J=8.46 Hz, 2H), 8.16 (s, 1H), 8.17 (s, 1H), 8.40 (d,J=2.57 Hz, 1H)

Example 252

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.62 Hz, 3H), 0.86 (dd, J=9.74,6.80 Hz, 9H), 0.91 (d, J=6.62 Hz, 4H), 0.99 (m, 1H), 1.16 (s, 1H), 1.34(m, 2H), 1.87 (d, J=10.66 Hz, 1H), 2.03 (m, 1H), 2.50 (dd, J=13.60,11.40 Hz, 1H), 2.63 (m, 1H), 2.97 (s, 3H), 3.12 (m, 4H), 3.44 (dd,J=14.71, 3.68 Hz, 1H), 3.75 (m, 1H), 3.83 (d, J=11.40 Hz, 1H), 4.12 (m,2H), 4.35 (d, J=15.81 Hz, 1H), 4.57 (m, 3H), 4.77 (d, J=9.93 Hz, 2H),7.09 (m, 3H), 7.17 (m, 2H), 7.22 (d, J=7.72 Hz, 1H), 7.78 (m, 4H), 7.83(d, J=8.82 Hz, 2H), 8.14 (s, 1H)

Example 253

¹H NMR (300 MHz, CD₃OD) δ ppm 0.87 (m, 6H), 0.92 (s, 9H), 2.02 (m, 1H),2.29 (q, J=9.19 Hz, 1H), 2.45 (dd, J=13.60, 11.40 Hz, 1H), 3.11 (m, 9H),3.43 (dd, J=14.71, 3.31 Hz, 1H), 3.73 (m, 1H), 3.99 (s, 1H), 4.07 (m,1H), 4.39 (d, J=15.81 Hz, 1H), 4.56 (d, J=15.44 Hz, 1H), 4.70 (s, 2H),7.12 (m, 5H), 7.22 (d, J=7.72 Hz, 1H), 7.45 (d, J=8.09 Hz, 1H), 7.81 (m,5H), 8.14 (s, 1H)

Example 254

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.25 Hz, 3H), 0.85 (dd,J=15.08, 6.99 Hz, 6H), 0.91 (d, J=6.62 Hz, 3H), 1.00 (m, 1H), 1.32 (m,1H), 1.85 (m, 1H), 2.03 (m, 1H), 2.51 (m, 2H), 3.09 (m, 8H), 3.44 (dd,J=14.71, 3.31 Hz, 1H), 3.75 (m, 1H), 3.85 (d, J=11.03 Hz, 1H), 4.11 (dd,J=0.11, 7.91 Hz, 1H), 4.36 (d, J=15.44 Hz, 1H), 4.54 (d, J=15.08 Hz,1H), 7.04 (m, 3H), 7.14 (m, 2H), 7.42 (d, J=7.72 Hz, 1H), 7.50 (t,J=7.91 Hz, 1H), 7.61 (d, J=3.31 Hz, 1H), 7.78 (d, J=8.82 Hz, 2H), 7.84(d, J=8.46 Hz, 2H), 7.88 (m, 2H), 7.98 (d, J=9.56 Hz, 1H), 8.14 (s, 1H)

Example 255

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.62 Hz, 3H), 0.82 (t, J=7.35Hz, 3H), 0.87 (d, J=6.99 Hz, 3H), 0.91 (d, J=6.62 Hz, 3H), 0.99 (m, 1H),1.33 (m, 1H), 1.85 (s, 1H), 2.01 (m, 1H), 2.47 (dd, J=13.79, 11.21 Hz,1H), 2.57 (m, 1H), 3.06 (m, 8H), 3.45 (dd, J=14.71, 3.31 Hz, 1H), 3.75(m, 1H), 3.85 (d, J=11.40 Hz, 1H), 4.11 (m, 1H), 4.40 (d, J=15.08 Hz,1H), 4.57 (d, J=15.08 Hz, 1H), 7.03 (dd, J=6.43, 3.86 Hz, 3H), 7.14 (m,2H), 7.47 (d, J=7.72 Hz, 1H), 7.56 (m, 2H), 7.77 (d, J=8.46 Hz, 2H),7.83 (d, J=8.82 Hz, 2H), 7.88 (m, 1H), 7.98 (m, 2H), 8.11 (m, 1H), 8.14(s, 1H), 8.67 (d, J=4.41 Hz, 1H)

Example 256

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (d, J=7.72 Hz, 6H), 0.91 (s, 9H),2.00 (d, J=6.25 Hz, 1H), 2.22 (q, J=9.07 Hz, 1H), 2.43 (m, 1H), 2.50 (s,3H), 3.10 (m, 10H), 3.42 (dd, J=14.71, 3.31 Hz, 1H), 3.72 (m, 1H), 3.98(s, 1H), 4.06 (d, J=10.66 Hz, 1H), 4.54 (t, J==15.08 Hz, 2H), 7.06 (m,5H), 7.54 (s, 1H), 7.77 (d, J=8.46 Hz, 1H), 7.83 (d, J=8.46 Hz, 1H),7.96 (d, J=9.19 Hz, 1H), 8.14 (s, 1H)

Example 257

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.62 Hz, 3H), 0.90 (d, J=6.62Hz, 3H), 0.95 (s, 9H), 1.88 (m, 1H), 2.93 (m, 8H), 3.34 (m, 1H), 3.83(m, 1H), 3.89 (s, 3H), 3.94 (d, J=3.31 Hz, 1H), 4.00 (s, 1H), 4.15 (m,1H), 4.63 (d, J=15.44 Hz, 1H), 4.83 (d, J=15.44 Hz, 1H), 6.21 (d, J=8.82Hz, 1H), 7.09 (m, 5H), 7.25 (m, 1H), 7.71 (d, J=8.82 Hz, 2H), 7.79 (d,J=8.46 Hz, 2H), 8.03 (m, 1H), 8.18 (s, 1H), 8.40 (dd, J=4.78, 1.47 Hz,1H)

Example 258

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (t, J=5.52 Hz, 3H), 0.84 (dd,J=12.50, 6.99 Hz, 6H), 0.90 (d, J=6.25 Hz, 3H), 0.97 (m, 1H), 1.33 (m,1H), 1.85 (m, 1H), 1.97 (m, J=8.82 Hz, 1H), 2.34 (s, 3H), 2.59 (s, 3H),2.97 (m, 8H), 3.79 (m, 3H), 4.20 (m, 1H), 4.39 (d, J=14.71 Hz, 1H), 4.48(d, J=14.71 Hz, 1H), 6.52 (d, J=8.46 Hz, 1H), 6.97 (d, J=5.15 Hz, 1H),7.20 (m, 5H), 7.70 (d, J=8.46 Hz, 2H), 7.79 (d, J=8.82 Hz, 2H), 8.16 (s,1H), 8.30 (d, J=5.15 Hz, 2H)

Example 259

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.62 Hz, 3H), 0.85 (m, 6H),0.91 (d, J=6.62 Hz, 3H), 1.00 (m, 1H), 1.32 (m, 1H), 1.86 (m, 1H), 2.02(m, 1H), 2.47 (m, 3H), 3.08 (m, 7H), 3.44 (dd, J=14.89, 3.49 Hz, 1H),3.75 (m, 1H), 3.85 (d, J=11.03 Hz, 1H), 4.11 (m, 1H), 4.30 (d, J=14.71Hz, 1H), 4.48 (d, J=14.71 Hz, 1H), 6.79 (d, J=1.84 Hz, 1H), 7.04 (m,3H), 7.13 (m, 2H), 7.19 (d, J=7.72 Hz, 1H), 7.37 (m, 1H), 7.49 (m, 1H),7.55 (m, 1H), 7.78 (d, J=8.46 Hz, 2H), 7.84 (d, J=8.82 Hz, 2H), 7.88 (m,1H, 7.96 (d, J=9.56 Hz, 1H), 8.14 (s, 1H)

Example 260

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.62 Hz, 3H), 0.82 (t, J=7.35Hz, 3H), 0.88 (d, J=6.62 Hz, 3H), 0.91 (d, J=6.62 Hz, 3H), 1.00 (m, 2H),1.31 (m, 1H), 1.86 (m, 1H), 2.00 (m, 1H), 2.51 (m, 2H), 3.07 (m, 8H),3.75 (m, 1H), 3.85 (d, J=11.03 Hz, 1H), 4.11 (m, 1H), 4.39 (d, J=15.08Hz, 1H), 4.57 (d, J=15.08 Hz, 1H), 7.04 (m, 3H), 7.13 (m, 2H), 7.44 (d,J=7.72 Hz, 1H), 7.56 (t, J=7.54 Hz, 1H), 7.66 (m, 2H), 7.77 (d, J=8.46Hz, 2H), 7.83 (d, J=8.46 Hz, 2H), 7.97 (d, J=9.93 Hz, 1H), 8.14 (s, 1H),9.06 (s, 1H), 9.14 (s, 1H)

Example 261

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.62 Hz, 3H), 0.85 (dd,J=16.18, 6.99 Hz, 6H), 0.91 (d, J=6.62 Hz, 3H), 0.97 (m, 1H), 1.28 (m,1H), 1.83 (s, 1H), 2.01 (m, 1H), 2.51 (m, 2H), 3.08 (m, 8H), 3.44 (m,1H), 3.74 (m, 1H), 3.84 (m, 1H), 3.90 (s, 3H), 4.12 (m, 1H), 4.24 (m,1H), 4.39 (d, J=15.08 Hz, 1H), 6.81 (d, J=8.46 Hz, 1H), 7.06 (m, 3H),7.15 (m, 2H), 7.63 (dd, 8.64, 2.39 Hz, 1H), 7.78 (m, 2H), 7.84 (d,J=8.82 Hz, 2H), 8.08 (d, J=1.84 Hz, 1H), 8.14 (s, 1H)

Example 262

¹H NMR (300 MHz, CD₃OD) δ ppm 0.87 (m, 6H), 0.92 (s, 9H), 2.03 (d,J=6.25 Hz, 1H), 2.22 (t, J=8.46 Hz, 1H), 2.43 (m, 1H), 3.09 (m, 9H),3.42 (m, 1H), 3.74 (m, 1H), 4.00 (s, 1H), 4.05 (m, 1H), 4.58 (s, 2H),7.08 (m, 5H), 7.60 (s, 1H), 7.77 (d, J=8.46 Hz, 2H), 7.84 (d, J=6.62 Hz,2H), 8.14 (s, 1H), 8.62 (d, J=2.57 Hz, 1H), 9.37 (s, 1H)

Example 263

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (d, J=7.72 Hz, 6H), 0.92 (s, 9H),1.53 (d, J=4.04 Hz, 6H), 2.00 (m, 1H), 2.24 (m, 1H), 2.44 (dd, J=13.60,11.77 Hz, 1H), 3.12 (m, 10H), 3.42 (dd, J=14.71, 3.31 Hz, 1H), 3.73 (m,1H), 3.98 (s, 1H), 4.08 (m, 1H), 4.38 (d, J=15.44 Hz, 1H), 4.62 (d,J=15.44 Hz, 1H), 7.11 (m, 5H), 7.53 (d, J=8.09 Hz, 1H), 7.77 (m, 3H),7.84 (d, J=8.46 Hz, 2H), 8.14 (s, 1H)

Example 264

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.62 Hz, 3H), 0.85 (t, J=7.35Hz, 3H), 1.00 (d, J=22.43 Hz, 2H), 1.26 (s, 4H), 1.58 (s, 8H), 1.99 (s,1H), 2.11 (m, 1H), 2.98 (m, 8H), 3.81 (m, 3H), 4.24 (m, 2H), 4.43 (d,J=15.44 Hz, 1H), 652 (d, J=8.82 Hz, 1H), 7.17 (m, 5H), 7.45 (d, J=6.62Hz, 1H), 7.70 (d, J=8.46 Hz, 2H), 7.78 (d, J=8.46 Hz, 2H), 8.16 (s, 1H),8.25 (s, 1H), 8.43 (d, J=3.68 Hz, 1H)

Example 265

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.92 (d, J=6.62Hz, 3H), 0.96 (s, 9H), 1.85 (dd, J=14.34, 6.99 Hz, 1H), 2.56 (s, 3H),2.69 (dd, J=13.97, 10.30 Hz, 1H), 3.02 (m, 7H), 3.31 (m, 1H), 3.77 (d,J=3.68 Hz, 2H), 4.00 (s, 1H), 4.20 (m, 2H), 4.42 (d, J=14.71 Hz, 1H),6.18 (d, J=9.19 Hz, 1H), 7.14 (m, 5H), 7.51 (dd, J=7.72, 2.21 Hz, 1H),7.72 (d, J=8.46 Hz, 2H), 7.80 (d, J=8.46 Hz, 2H), 7.87 (m, 1H), 8.17 (s,1H), 8.42 (m, 1H)

Example 266

¹H NMR (300 MHz, CDCl₃) δ ppm 0.89 (t, J=6.62 Hz, 6H), 0.98 (m, 9H),1.88 (m, 1H), 2.95 (m, 8H), 3.41 (m, 1H), 3.88 (m, 2H), 4.04 (d, J=3.31Hz, 1H), 4.29 (m, 2H), 4.51 (d, J=16.18 Hz, 1H), 6.42 (d, J=9.19 Hz,1H), 7.15 (m, 5H), 7.36 (dd, J=5.15, 2.57 Hz, 1H), 7.70 (d, J=8.46 Hz,2H), 7.80 (m, 2H), 8.16 (s, 1H), 9.15 (m, 2H)

Example 267

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.62 Hz, 3H), 0.88 (m, 9H),1.00 (m, 1H), 1.35 (m, 1H), 1.86 (m, 1H), 1.98 (m, 1H), 2.77 (dd,J=14.34, 10.30 Hz, 1H), 2.88 (dd, J=13.60, 6.99 Hz, 1H), 3.09 (m, 7H),3.82 (m, 3H), 4.23 (m, 2H), 4.50 (d, J=16.18 Hz, 1H), 6.54 (d, J=8.82Hz, 1H), 7.18 (m, 5H), 7.34 (dd, J=5.15, 2.21 Hz, 1H), 7.70 (d, J=8.82Hz, 2H), 7.79 (d, J=8.46 Hz, 2H), 8.16 (s, 1H), 9.15 (m, 2H)

Example 268

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.62 Hz, 3H), 0.84 (m, 6H),0.89 (d, J=6.62 Hz, 3H), 0.98 (m, 1H), 1.33 (m, 1H), 1.86 (m, 1H), 1.98(m, 1H), 2.76 (dd, J=14.34, 10.30 Hz, 1H), 2.88 (m, 2H), 2.98 (m, 1H),3.17 (m, 6H), 3.84 (m, 1H), 3.93 (t, J=3.86 Hz, 1H), 4.21 (m, 1H), 4.59(d, J=15.44 Hz, 1H), 4.75 (d, J=15.81 Hz, 1H), 6.54 (d, J=8.82 Hz, 1H),7.18 (m, 5H), 7.49 (m, 2H), 7.70 (d, J=8.46 Hz, 2H), 7.79 (d, J=8.46 Hz,2H), 8.16 (s, 1H), 8.34 (s, 1H)

Example 269

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.25 Hz, 3H), 0.84 (m, 6H),0.90 (d, J=6.62 Hz, 3H), 0.97 (m, 1H), 1.29 (m, 1H), 1.93 (m, 2H), 2.76(dd, J=14.52, 10.48 Hz, 1H), 3.05 (m, 8H), 3.77 (d, J=11.03 Hz, 1H),3.87 (s, 3H), 3.87 (m, 2H), 4.14 (m, 1H), 4.58 (d, J=15.08 Hz, 1H), 4.85(d, J=15.44 Hz, 1H), 6.44 (d, J=8.46 Hz, 1H), 7.14 (m, 5H), 7.25 (dd,J=8.09, 4.78 Hz, 1H), 7.70 (d, J=8.46 Hz, 2H), 7.79 (d, J=8.46 Hz, 2H),8.01 (dd, J=8.09, 1.47 Hz, 1H), 8.18 (s, 1H), 8.40 (dd, J=4.78, 1.47 Hz,1H)

Example 270

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (s, 1H),2.13 (d, J=21.02 Hz, 1H), 2.93 (td, J=8.82, 7.12 Hz, 2H), 3.14 (m, 9H),3.63 (d, J=10.51 Hz, 1H), 3.78 (s, 1H), 4.15 (s, 1H), 4.40 (d, J=14.92Hz, 1H), 4.48 (d, J=15.26 Hz, 1H), 6.52 (d, J=8.14 Hz, 1H), 6.96 (s,1H), 7.19 (m, 5H), 7.70 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),8.16 (s, 1H)

Example 273

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.44 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.40 (m, 1H), 2.04 (m, 2H), 2.52 (dd,J=13.90, 11.53 Hz, 1H), 2.67 (m, 1H), 2.81 (s, 3H), 3.09 (m, 4H), 3.47(dd, J=14.92, 3.73 Hz, 1H), 3.75 (m, 2H), 4.14 (m, 1H), 4.37 (d, J=15.60Hz, 1H), 4.55 (s, 2H), 4.64 (d, J=15.60 Hz, 1H), 4.80 (s, 1H), 7.15 (m,5H), 7.51 (s, 1H), 7.77 (d, J=8.48 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H),7.95 (d, J=9.83 Hz, 1H), 8.14 (s, 1H)

Example 274

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (m, 6H), 1.73 (s, 1H), 2.15 (m, 4H),2.54 (m, 2H), 2.69 (s, 3H), 2.81 (dd, J=14.58, 8.82 Hz, 1H), 2.97 (d,J=14.92 Hz, 1H), 3.17 (m, 4H), 3.40 (m, 2H), 3.68 (m, 4H), 3.88 (m, 1H),4.11 (s, 2H), 442 (s, 2H), 7.13 (m, 5H), 7.20 (s, 1H), 7.83 (d, J=8.82Hz, 2H), 7.88 (m, 2H), 8.04 (m, 1H), 8.16 (s, 1H)

Example 275

¹H NMR (300 MHz, CDCl₃) δ ppm 0.66 (d, J=6.78 Hz, 3H) 0.74 (d, J=6.78Hz, 3H) 0.86 (t, J=6.44 Hz, 6H) 1.88 (dd, J=13.73, 6.95 Hz, 1H) 2.29 (m,1H) 2.68 (s, 3H) 2.79 (dd, J=14.07, 10.00 Hz, 1H) 2.94 (t, J=6.78 Hz,1H) 3.08 (dd, J=14.07, 4.92 Hz, 1H) 3.17 (m, 2H) 3.90 (m, 1H) 4.03 (d,J=10.51 Hz, 1H) 4.18 (m, 1H) 4.88 (s, 2H) 6.22 (d, J=3.05 Hz, 1H) 6.33(d, J=2.71 Hz, 1H) 6.94 (s, 1H) 7.08 (m, 3H) 7.43 (m, 2H) 7.61 (m, 1H)7.66 (d, J=8.48 Hz, 2H) 7.78 (m, 2H) 7.83 (d, J=7.46 Hz, 1H) 8.13 (s,1H)

Example 276

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.86 (m, 1H),2.16 (m, 1H), 2.97 (m, 10H), 3.66 (d, J=10.85 Hz, 1H), 3.82 (d, J=5.43Hz, 1H), 4.18 (d, J=14.92 Hz, 2H), 4.31 (d, J=14.92 Hz, 1H), 6.63 (m,5H), 7.16 (m, 5H), 7.70 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),8.15 (s, 1H)

Example 277

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.78 Hz, 3H), 0.84 (m, 6H),0.88 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 0.97 (dd, J=8.14, 5.76Hz, 1H), 1.30 (m, 1H), 1.85 (s, 1H), 2.03 (d, J=7.12 Hz, 1H), 2.51 (dd,J=13.90, 11.53 Hz, 1H), 2.67 (m, 1H), 3.09 (m, 5H), 3.45 (dd, J=14.75,3.56 Hz, 1H), 3.75 (m, 1H), 3.82 (d, J=11.19 Hz, 1H), 4.13 (s, 1H), 4.28(d, J=15.94 Hz, 1H), 4.52 (d, J=15.60 Hz, 1H), 7.12 (m, 3H), 7.17 (m,2H), 7.56 (m, 1H), 7.78 (d, J=8.82 Hz, 2H), 7.84 (d, J=8.48 Hz, 2H),7.97 (m, 1H), 8.14 (s, 1H), 8.28 (m, 1H), 8.31 (s, 1H)

Example 278

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.86 (m, 6H),0.91 (d, J=6.44 Hz, 3H), 1.00 (m, 1H), 1.33 (m, 1H), 1.87 (s, 1H), 2.03(m, 1H), 2.53 (dd, J=13.90, 11.19 Hz, 1H), 2.76 (m, 1H), 3.09 (m, 8H),3.46 (dd, J=14.92, 3.39 Hz, 1H), 3.76 (m, 1H), 3.82 (d, J=11.19 Hz, 1H),4.11 (d, J=6.78 Hz, 1H), 4.28 (d, J=16.62 Hz, 1H), 4.55 (d, J=16.28 Hz,1H), 7.16 (m, 5H), 7.45 (d, J=7.12 Hz, 1H), 7.78 (d, J=8.48 Hz, 2H),7.84 (d, J=8.48 Hz, 2H), 7.97 (m, 1H), 8.14 (s, 1H), 8.31 (d, J=7.12 Hz,2H)

Example 279

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.85 (m, 6H),0.91 (d, J=6.44 Hz, 3H), 0.97 (d, J=9.16 Hz, 1H), 1.32 (m, 1H), 1.84 (s,1H), 1.99 (d, (14.58 Hz, 1H), 2.52 (dd, J=14.07, 11.36 Hz, 1H), 2.72 (m,1H), 3.10 (m, 9 μl, 3.47 (dd, J=14.92, 3.73 Hz, 1H), 3.76 (m, 1H), 3.82(d, J=11.19 Hz, 1H), 4.14 (d, J=10.85 Hz, 1H), 4.36 (d, J=15.60 Hz, 1H),4.47 (s, 2H), 4.63 (d, J=15.94 Hz, 1H), 7.15 (m, 5H), 7.47 (s, 1H), 7.78(d, J=8.82 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H), 7.94 (d, J=9.49 Hz, 1H),8.14 (s, 1H)

Example 280

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.85 (t, J=7.12Hz, 3H), 0.97 (m, 1H), 1.29 (s, 1H), 1.67 (m, J=18.65 Hz, 1H), 1.81 (dd,J=10.34, 6.61 Hz, 4H), 2.02 (d, J=10.85 Hz, 2H), 2.52 (m, 1H), 2.61 (m,1H), 2.71 (d, J=7.80 Hz, 1H), 3.11 (m, 6H), 3.36 (m, 1H), 3.45 (m, 1H),3.75 (d, J=6.44 Hz, 1H), 3.84 (d, J=10.85 Hz, 1H), 4.14 (s, 1H), 4.36(d, J=15.26 Hz, 1H), 4.47 (s, 2H), 4.63 (d, J=15.94 Hz, 1H), 7.16 (m,5H), 7.47 (s, 1H), 7.78 (d, J=8.48 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H),7.94 (d, J=9.16 Hz, 1H), 8.15 (s, 1H)

Example 281

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.84 (t, J=7.29Hz, 3H), 0.97 (m, 1H), 1.17 (m, 1H), 1.32 (m, 3H), 1.58 (m, 6H), 1.85(s, 1H), 2.26 (m, 1H), 2.53 (dd, J=13.73, 11.36 Hz, 1H), 2.70 (m, 1H),3.14 (m, 6H), 3.48 (dd, J=14.92, 4.07 Hz, 1H), 3.78 (dd, J=11.19, 4.75Hz, 1H), 3.83 (d, J=11.19 Hz, 1H), 4.15 (s, 1H), 4.36 (d, J=15.60 Hz,1H), 4.47 (s, 2H), 4.63 (d, J=15.94 Hz, 1H), 7.16 (m, 5H), 7.47 (s, 1H),7.78 (d, J=8.82 Hz, 2H), 7.84 (d, J=8.48 Hz, 2H), 7.94 (d, J=9.49 Hz,1H), 8.14 (s, 1H)

Example 282

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (m, 6H) 0.87 (d, J=6.78 Hz, 3H) 0.91(d, J=6.78 Hz, 3H) 0.97 (m, 1H) 1.16 (m, 1H) 1.98 (m, 2H) 2.24 (s, 3H)2.56 (dd, J=13.90, 10.85 Hz, 1H) 2.98 (m, 1H) 3.10 (m, 3H) 3.43 (dd,J=14.92, 2.37 Hz, 1H) 3.77 (m, 1H) 4.05 (m, 1H) 4.16 (d, J=10.85 Hz, 1H)4.81 (m, J=9.49 Hz, 2H) 4.86 (m, 1H) 4.95 (m, 1H) 6.38 (m, 1H) 6.42 (d,J=3.05 Hz, 1H) 6.99 (m, 3H) 7.07 (m, 2H) 7.19 (dd, J=5.09, 1.70 Hz, 1H)7.76 (s, 1H) 7.79 (m, 1H) 7.86 (d, J=8.82 Hz, 2H) 8.17 (d, J=8.48 Hz,2H) 8.48 (d, J=5.09 Hz, 1H)

Example 283

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.84 (t, J=7.29Hz, 3H), 0.95 (d, J=16.28 Hz, 1H), 1.08 (d, J=6.10 Hz, 6H), 1.31 (m,3H), 1.59 (d, J=16.95 Hz, 6H), 1.89 (s, 1H), 2.27 (m, 1H), 2.48 (m, 1H),2.57 (m, 1H), 2.86 (m, 1H), 3.13 (m, 9H), 3.46 (dd, J=14.75, 3.90 Hz,1H), 3.77 (m, 1H), 3.82 (d, J=11.19 Hz, 1H), 4.07 (s, 2H), 4.11 (m, 1H),4.44 (m, 2H), 7.12 (m, 5H), 7.30 (s, 1H), 7.77 (d, J=8.48 Hz, 2H), 7.83(d, J=8.48 Hz, 2H), 8.14 (s, 1H)

Example 284

¹H NMR (300 MHz, CD₃OD) δ ppm 0.55 (m, 2H), 0.63 (m, 3H), 0.71 (d,J=6.44 Hz, 3H), 1.08 (d, J=6.44 Hz, 6H), 1.22 (s, 3H), 1.61 (m, 6H),2.29 (m, 1H), 2.52 (dd, J=14.24, 11.53 Hz, 1H), 2.84 (m, 1H), 3.20 (m,9H), 3.44 (m, 1H), 3.60 (m, 1H), 3.79 (d, J=11.19 Hz, 1H), 4.01 (s, 2H),4.10 (m, 1H), 4.28 (d, J=15.94 Hz, 1H), 4.42 (d, J=15.94 Hz, 1H), 7.17(m, 5 H), 7.24 (s, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.81 (d, J=8.82 Hz,2H), 8.13 (s, 1H)

Example 285

¹H NMR (300 MHz, CD₃OD) δ ppm 0.72 (d, J=6.44 Hz, 3H), 0.86 (dd,J=12.72, 6.95 Hz, 6H), 0.91 (d, J=6.44 Hz, 3H), 0.99 (m, 1H), 1.32 (m,1H), 1.85 (m, 1H), 2.02 (m, 1H), 2.51 (m, 2H), 3.07 (m, 9H), 3.44 (dd,J=14.92, 3.39 Hz, 1H), 3.75 (m, 1H), 3.83 (d, J=11.19 Hz, 1H), 4.13 (m,1H), 4.29 (d, J=14.92 Hz, 1H), 4.49 (d, J=14.92 Hz, 1H), 7.06 (m, 3H),7.15 (m, 2H), 7.38 (t, J=3.05 Hz, 1H), 7.38 (m, 2H), 7.59 (m, 2H), 7.78(d, J=8.82 Hz, 2H), 7.84 (d, J=8.82 Hz, 2H), 7.89 (s, 1H), 8.14 (s, 1H)

Example 286

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.85 (dd, J=8.99,6.95 Hz, 6H), 0.91 (t, J=5.76 Hz, 3H), 1.00 (m, 1H), 1.26 (s, 1H), 1.38(m, 1H), 1.53 (s, 1H), 1.87 (m, 1H), 1.98 (m, 1H), 2.87 (m, 3H), 3.15(m, 5H), 3.82 (m, 3H), 4.17 (m, 1H), 4.37 (d, J=15.60 Hz, 1H), 4.59 (d,J=15.60 Hz, 1H), 4.74 (d, J=4.75 Hz, 2H), 6.53 (d, J=8.82 Hz, 1H), 7.17(m, 6H), 7.66 (m, 1H), 7.70 (d, J=6.78 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),7.97 (s, 1H), 8.15 (s, 1H)

Example 287

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.85 (t, J=6.27Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 1.03 (dd, J=12.55, 9.16 Hz, 1H), 1.52(s, 1H), 1.86 (s, 1H), 1.99 (m, 1H), 2.86 (m, 4H), 3.14 (m, 5H), 3.78(m, J=10.85 Hz, 2H), 3.88 (d, J=3.73 Hz, 1H), 4.12 (d, J=7.12 Hz, 1H),4.16 (s, 1H), 4.41 (d, J=15.94 Hz, 1H), 4.58 (d, J=15.60 Hz, 1H), 6.53(m, 1H), 7.19 (m, 6H), 7.66 (m, 3H), 7.79 (d, J=8.82 Hz, 2H), 8.15 (s,1H), 8.20 (s, 1H)

Example 288

¹H NMR (300 MHz, CD₃OD) δ ppm 0.88 (d, J=6.99 Hz, 6H), 0.92 (s, 9H),1.47 (dd, J=6.62, 1.84 Hz, 3H), 2.02 (m, 1H), 2.29 (m, 1H), 2.45 (t,J=12.13 Hz, 1H), 3.09 (m, 10H), 3.43 (dd, J=15.08, 3.31 Hz, 1H), 3.73(m, 1H), 3.99 (s, 1H), 4.07 (m, 1H), 4.38 (d, J=15.44 Hz, 1H), 4.59 (d,J=15.44 Hz, 1H), 7.15 (m, 5H), 7.45 (dd, J=7.72, 2.21 Hz, 1H), 7.81 (m,6H), 8.14 (s, 1H)

Example 363

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.83 (d,J=6.44 Hz, 1H), 2.09 (m, 1H), 2.68 (dd, J=14.24, 10.85 Hz, 1H), 2.84(dd, J=13.56, 6.44 Hz, 1H) 3.02 (m, 4H), 3.21 (m, 1H), 3.32 (d, J=17.97Hz, 1H), 3.61 (d, J=17.97 Hz, 1H), 3.87 (m, J=10.85 Hz, 2H), 4.25 (m,1H), 4.70 (t, J=14.92 Hz, 2H), 6.08 (d, J=9.16 Hz, 1H), 7.09 (m, 5H),7.53 (m, 1H), 7.56 (d, J=2.37 Hz, 1H), 7.72 (d, J=8.48 Hz, 2H), 7.79 (d,J=8.48 Hz, 2H), 8.16 (dd, J=8.99, 1.53 Hz, 1H), 8.17 (s, 1H), 8.24 (d,J=2.03 Hz, 1H)

Example 364

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (J=6.44 Hz, 3H), 0.82 (d, J=6.78 Hz,3H), 0.86 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 2.02 (m, 2H),2.50 (dd, J=13.90, 11.53 Hz, 1H), 2.95 (m, 1H), 3.09 (m, 5H), 3.21 (dd,J=13.90, 3.73 Hz, 1H), 3.44 (dd, J=14.92, 3.39 Hz, 1H), 3.78 (m, 2H),3.96 (s, 3H), 4.02 (d, J=10.85 Hz, 1H), 4.14 (m, 1H), 4.95 (d, J=16.28Hz, 1H), 5.02 (d, J=16.28 Hz, 1H), 7.01 (m, 3H), 7.15 (m, 2H), 7.27 (m,2H), 7.51 (d, J=7.80 Hz, 1H), 7.59 (d, J=7.46 Hz, 1H), 7.76 (d, J=8.82Hz, 2H), 7.82 (d, J=8.82 Hz, 1H), 8.13 (s, 1H).

Example 365

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (d, J=6.44 Hz, 3H), 0.86 (d, J=6.44Hz, 3H), 0.89 (d, J=3.39 Hz, 3H), 0.92 (d, J=3.39 Hz, 3H), 1.85 (d,J=7.12 Hz, 1H), 2.16 (m, 1H), 2.70 (dd, J=14.24, 10.51 Hz, 1H), 2.84(dd, J=13.56, 6.78 Hz, 1H), 3.00 (m, 1H), 3.07 (m, 2H), 3.21 (m, 1H),3.45 (d, J=17.63 Hz, 1H), 3.76 (m, 2H), 3.84 (d, J=3.05 Hz, 1H), 3.92(d, Hz, 1H), 4.25 (m, 1H), 4.94 (d, J=15.94 Hz, 1H), 5.03 (d, J=16.28Hz, 1H), 6.20 (d, J=9.16 Hz, 1H), 7.16 (m, 5H), 7.32 (d, J=8.48 Hz, 1H),7.49 (t, J=7.46 Hz, 1H), 7.64 (m, 1H), 7.72 (d, J=8.48 Hz, 2H), 7.79 (m,2H), 7.82 (d, J=7.46 Hz, 1H), 7.95 (d, J=8.82 Hz, 1H), 8.12 (d, J=8.48Hz, 1H), 8.16 (s, 1H).

Example 366

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (d, J=6.44 Hz, 3H), 0.75 (d, J=6.78Hz, 3H), 0.82 (d, J=6.44 Hz, 6H), 1.96 (m, 1H), 2.37 (dd, J=13.05, 11.70Hz, 1H), 3.01 (m, 8H), 3.59 (d, J=7.12 Hz, 1H), 3.85 (m, 1H), 3.91 (s,3H), 4.02 (d, J=10.85 Hz, 1H), 5.01 (d, J=5.09 Hz, 2H), 6.98 (m, 1H),7.12 (d, J=4.07 Hz, 5H), 7.23 (dd, J=8.14, 4.75 Hz, 1H), 7.77 (d, J=8.82Hz, 2H), 7.81 (d, J=8.82 Hz, 2H), 7.89 (m, 1H), 8.24 (s, 1H), 8.33 (dd,J=4.75, 1.36 Hz, 1H).

Example 367

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.83 (s, 1H),2.06 (m, 1H), 2.65 (dd, J=14.24, 10.51 Hz, 1H), 2.82 (m, 1H), 3.04 (m,3H), 3.20 (m, 2H), 3.54 (d, J=17.97 Hz, 1H), 3.85 (d, J=11.19 Hz, 2H),4.22 (s, 1H), 4.51 (d, J=2.37 Hz, 2H), 5.92 (s, 2H), 6.06 (d, J=9.49 Hz,1H), 6.75 (d, J=7.80 Hz, 1H), 6.91 (m, 2H), 7.07 (m, 5H), 7.72 (d,J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H).

Example 368

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=2.71 Hz, 3H), 0.91 (d, J=3.05Hz, 3H), 1.86 (dd, J=14.07, 7.29 Hz, 1H), 2.99 (m, 6H), 3.45 (d, J=17.29Hz, 1H), 3.67 (m, 1H), 3.73 (d, J=12.21 Hz, 1H), 3.90 (m, 1H), 3.98 (d,J=16.28 Hz, 1H), 4.20 (s, 1H), 4.63 (s, 2H), 6.13 (d, J=8.82 Hz, 1H),7.13 (dd, J=6.78, 2.71 Hz, 2H), 7.22 (m, 3H), 7.31 (m, 2H), 7.39 (m,3H), 7.73 (d, J=8.48 Hz, 2H), 7.80 (m, 2H), 8.16 (s, 1H)

Example 369

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (s, 1H),2.09 (s, 1H), 3.00 (m, 6H), 3.49 (d, J=17.97 Hz, 1H), 3.69 (d, J=17.97Hz, 1H), 3.92 (m, J=10.51 Hz, 2H), 4.28 (s, 1H), 4.71 (m, 2H), 6.45 (d,J=7.80 Hz, 1H), 7.14 (m, 5H), 7.51 (m, 2H), 7.70 (d, J=8.48 Hz, 2H),7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H), 8.66 (s, 2H)

Example 370

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=3.73 Hz, 3H), 0.79 (d, J=3.39Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 2.01 (m, 2H),2.40 (s, 6H), 2.45 (m, 1H), 3.03 (m, 4H), 3.21 (dd, J=13.73, 3.56 Hz,2H), 3.45 (dd, J=14.75, 3.56 Hz, 1H), 3.69 (d, Hz, 1H), 3.76 (m, 1H),3.90 (s, 2H), 4.00 (d, J=11.19 Hz, 1H), 4.11 (m, 1H), 4.75 (m, 2H), 6.99(m, 3H), 7.12 (m, 2H), 7.42 (s, 1H), 7.78 (m, 2H), 7.83 (d, J=8.82 Hz,2H), 8.14 (s, 1H)

Example 371

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.78 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (dd, J=14.58, 6.78 Hz, 1H), 2.09(m, 1H), 2.86 (dd, J=13.39, 6.95 Hz, 2H), 3.12 (m, 8H), 3.61 (d, J=17.63Hz, 1H), 3.83 (m, 1H), 3.92 (d, J=10.85 Hz, 1H), 4.23 (d, J=4.41 Hz,1H), 4.76 (m, 2H), 6.37 (s, 1H), 7.05 (s, 1H), 7.13 (m, 5H), 7.72 (d,J=8.48 Hz, 2H), 7.80 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 372

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (d, J=4.07 Hz, 3H), 0.80 (d, J=3.73Hz, 3H), 1.23 (d, J=28.82 Hz, 2H), 1.63 (m, 6H), 2.02 (m, 1H), 2.27 (m,1H), 2.46 (m, 1H), 2.65 (s, 3H), 3.10 (m, 6H), 3.47 (dd, J=14.75, 3.90Hz, 1H), 3.69 (d, J=17.97 Hz, 1H), 3.79 (m, 1H), 4.01 (d, J=11.19 Hz,1H), 4.16 (m, 1H), 4.73 (m, 2H), 6.98 (m, 3H), 7.13 (dd, J=6.44, 3.05Hz, 2 H), 7.24 (s, 1H), 7.77 (d, J=8.82 Hz, 2H), 7.83 (d, J=8.82 Hz,2H), 8.14 (s, 1H)

Example 373

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (dd, J=6.78, 3.05 Hz, 6H), 0.86 (d,J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.87 (m, 1H), 2.13 (m, J=10.17Hz, 1H), 2.93 (m, 5H), 3.20 (m, 1H), 3.47 (d, J=18.31 Hz, 1H), 3.71 (d,J=17.97 Hz, 1H), 3.85 (s, 1H), 3.93 (d, J=10.51 Hz, 1H), 4.27 (s, 1H),4.85 (d, J=1.70 Hz, 2H), 6.38 (s, 1H), 7.17 (m, 5H), 7.26 (m, 2H), 7.71(m, J=8.48 Hz, 3H), 7.80 (d, J=8.82 Hz, 2H), 8.16 (s, 1H), 8.55 (s, 1H)

Example 374

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (dd, J=6.27, 4.58 Hz, 6H), 0.87 (d,J=6.78 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.85 (m, 1H), 2.13 (s, 1H),2.76 (m, 1H), 2.84 (m, 1H), 2.96 (s, 3H), 3.01 (m, 2H), 3.20 (m, 1H),3.40 (d, J=17.29 Hz, 1H), 3.69 (d, J=17.29 Hz, 2H), 3.84 (s, 1H), 3.91(d, J=10.51 Hz, 1H), 4.24 (s, 1H), 4.83 (m, 2H), 6.21 (s, 1H), 7.16 (s,5H), 7.24 (m, 1H), 7.72 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H),7.88 (s, 1H), 8.02 (s, 1H), 8.16 (s, 1H),

Example 375

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.86 (m, 1H),2.05 (m, 1H), 2.64 (dd, J=14.24, 10.85 Hz, 1H), 2.84 (m, 1H), 3.01 (m,3H), 3.20 (d, J=17.97 Hz, 1H), 3.54 (d, J=17.97 Hz, 1H), 3.81 (m, 1H),3.86 (d, J=11.19 Hz, 1H), 4.23 (m, J=4.41 Hz, 1H), 4.62 (m, 2H), 6.06(d, J=9.83 Hz, 1H), 7.02 (m, 5H), 7.32 (m, 4H), 7.41 (m, 2H), 7.72 (d,J=8.82 Hz, 2H), 7.79 (d, J=8.82 Hz, 2H), 8.16 (s, 1H)

Example 376

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.78 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 2.00 (m, 1H), 2.42 (dd, J=13.56, 11.87Hz, 1H), 2.59 (s, 3H), 3.02 (m, 6H), 3.20 (dd, J=13.73, 3.22 Hz, 1H),3.44 (dd, J=14.92, 3.39 Hz, 1H), 3.68 (d, J=17.97 Hz, 1H), 3.75 (m, 1H),4.01 (d, J=10.85 Hz, 1H), 4.11 (m, 1H), 4.73 (d, J=2.71 Hz, 2H), 6.88(m, 3H), 7.07 (m, 2H), 7.51 (t, J=7.63 Hz, 1H), 7.66 (d, J=8.14 Hz, 1H),7.77 (d, J=8.48 Hz, 2H), 7.82 (d, J=8.82 Hz, 2H), 7.94 (d, J=7.80 Hz,1H), 8.03 (s, 1H), 8.14 (s, 1H)

Example 377

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (dd, J=6.44, 4.75 Hz, 6H), 1.21 (m,2H), 1.59 (m, 8H), 2.01 (m, 1H), 2.27 (m, 1H), 2.46 (dd, J=13.56, 11.87Hz, 1H), 2.99 (d, J=17.97 Hz, 1H), 3.07 (m, 1H), 3.22 (m, 2H), 3.43 (m,3H), 3.48 (m, 1H), 3.69 (d, J=17.97 Hz, 1H), 3.79 (m, 1H), 4.01 (d,J=11.19 Hz, 1H), 4.14 (m, 1H), 4.66 (s, 2H), 4.77 (d, J=5.76 Hz, 2H),6.99 (m, 3H), 7.13 (m, 2H), 7.41 (s, 1H), 7.77 (d, J=8.82 Hz, 2H), 7.83(d, J=8.48 Hz, 2H), 8.14 (s, 1 H)

Example 378

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (m, 6H), 1.78 (m, 7H), 1.99 (m, 2H),2.47 (dd, J=13.73, 11.70 Hz, 1H), 2.60 (m, 1H), 2.66 (s, 3H), 3.00 (m,1H), 3.20 (m, 2H), 3.40 (m, 2H), 3.69 (d, J=18.31 Hz, 1H), 3.76 (m, 1H),4.02 (d, J=10.85 Hz, 1H), 4.13 (m, 1H), 4.73 (t, J=15.60 Hz, 2H), 6.99(m, 3H), 7.12 (m, 2H), 7.25 (s, 1H), 7.77 (d, J=8.48 Hz, 2H), 7.84 (d,J=4.75 Hz, 2H), 8.14 (s, 1H)

Example 379

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (t, J=6.27 Hz, 6H), 1.76 (m, 3H),2.00 (m, 4H), 2.46 (dd, J=13.39, 11.70 Hz, 1H), 2.62 (m, 1H), 3.00 (m,1H), 3.20 (m, 2H), 3.43 (m, 2H), 3.43 (s, 3H), 3.69 (d, J=18.31 Hz, 1H),3.76 (m, 1H), 4.01 (d, J=10.85 Hz, 1H), 4.11 (s, 1H), 4.66 (s, 2H), 4.77(d, J=5.76 Hz, 2H), 6.99 (m, 3H), 7.13 (dd, 6.27, 3.56 Hz, 2H), 7.41 (s,1H), 7.77 (d, J=8.82 Hz, 2H), 7.83 (d, J=8.82 Hz, 2H), 8.14 (s, 1H),8.22 (d, J=9.49 Hz, 1H)

Example 380

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.78 Hz, 3H), 0.83 (d, J=4.75Hz, 3H), 0.87 (m, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.86 (m, J=7.12 Hz, 1H),2.07 (m, 1H), 2.77 (m, 2H), 3.04 (m, 3H), 3.22 (m, 1H), 3.44 (d, J=18.31Hz, 1H), 3.66 (d, J=17.97 Hz, 1H), 3.88 (m, 2H), 4.28 (m, 1H), 4.63 (m,2H), 6.12 (d, J=9.49 Hz, 1H), 7.12 (m, 3H), 7.22 (m, 2H), 7.45 (m, 1H),7.70 (m, 4H), 7.82 (d, J=8.48 Hz, 2H), 8.17 (s, 1H)

Example 381

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (dd, J=8.48, 6.78 Hz, 6H), 0.87 (d,J=6.44 Hz, 3H), 0.93 (d, J=6.78 Hz, 2H), 1.84 (m, 1H), 2.09 (m, 1H),2.70 (s, 3H), 2.83 (d, J=13.56 Hz, 1H), 3.02 (m, 5H), 3.21 (m, 1H), 3.21(s, 1H), 3.36 (d, J=17.97 Hz, 1H), 3.65 (d, J=17.97 Hz, 1H), 3.86 (m,J=10.85 Hz, 2H), 4.30 (s, 1H), 4.67 (m, 2H), 6.15 (d, J=9.49 Hz, 1H),7.10 (d, J=7.12 Hz, 3H), 7.24 (s, 2H), 7.40 (s, 1H), 7.72 (d, J=8.48 Hz,2H), 7.79 (d, J=8.82 Hz, 2H), 7.95 (s, 1H), 8.16 (s, 1H)

Example 382

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.81 (m, 1H),2.06 (m, 1H), 2.64 (dd, J=14.41, 10.68 Hz, 1H), 2.83 (dd, J=13.56, 6.78Hz, 1H), 3.03 (m, 2H), 3.21 (m, 2H), 3.55 (d, J=17.97 Hz, 1H), 3.82 (m,2H), 3.86 (d, J=11.19 Hz, 1H), 4.24 (m, 1H), 4.33 (s, 2H), 4.62 (m, 2H),6.08 (d, J=9.16 Hz, 1H), 7.04 (m, 5H), 7.24 (s, 1H), 7.38 (m, 3H), 7.72(d, J=8.48 Hz, 2H), 7.79 (d, J=8.82 Hz, 2H), 8.16 (s, 1H)

Example 383

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 6H), 0.87 (d, J=6.44 Hz, 3H),0.93 (d, J=6.44 Hz, 3H), 1.18 (s, 1H), 1.84 (m, 2H), 2.70 (dd, J=14.24,10.51 Hz, 1H), 2.84 (dd, J=13.56, 6.44 Hz, 1H), 3.04 (m, 3H), 3.22 (m,1H), 3.41 (d, J=17.97 Hz, 1H), 3.61 (d, J=18.31 Hz, 2H), 3.85 (s, 1H),3.96 (d, J=11.19 Hz, 1H), 4.26 (s, 1H), 4.57 (d, J=15.26 Hz, 1H), 4.64(d, J=14.92 Hz, 1H), 6.14 (d, J=9.16 Hz, 1H), 7.11 (m, 5H), 7.26 (m,2H), 7.72 (d, J=8.48 Hz, 2 H), 7.79 (d, J=8.82 Hz, 2H), 8.17 (s, 1H),8.59 (s, 2H)

Example 384

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 4H), 0.82 (d, J=7.46Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.19 (s, 1H),1.85 (m, 2H), 2.64 (dd, J=14.07, 10.68 Hz, 1H), 2.86 (dd, J=13.56, 6.78Hz, 1H), 3.04 (m, 3H), 3.20 (m, 1H), 3.31 (d, J=17.63 Hz, 1H), 3.56 (d,J=17.97 Hz, 1H), 3.62 (s, 1H), 3.78 (s, 1H), 3.93 (d, J=11.19 Hz, 1H),4.23 (m, 1H), 4.63 (m, 2H), 6.12 (d, J=8.82 Hz, 1H), 7.05 (m, 5H), 7.32(s, 1H), 7.74 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.82 Hz, 2H), 8.09 (s, 1H),8.17 (s, 1H), 8.57 (s, 1H), 8.73 (s, 1 μl

Example 385

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=6.78 Hz, 3H), 0.76 (t, J=7.12Hz, 3H), 0.86 (m, 1H), 1.18 (m, 3H), 1.50 (m, 8H), 1.74 (s, 1H), 2.10(s, 3H), 2.23 (m, 1H), 2.37 (m, 1H), 3.06 (m, 3H), 3.62 (m, 1H), 3.77(d, J=18.31 Hz, 1H), 3.94 (d, J=9.49 Hz, 1H), 4.08 (d, J=11.19 Hz, 1H),4.58 (s, 2H), 5.00 (d, J=6.44 Hz, 1H), 6.90 (s, 1H), 6.97 (m, 3H), 7.05(m, 2H), 7.77 (d, J=8.82 Hz, 2H), 7.81 (d, J=8.82 Hz, 2H), 8.20 (d,J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 386

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62 (d, J=6.78 Hz, 3H), 0.76 (t, J=7.12Hz, 3H), 0.81 (dd, J=6.61, 1.87 Hz, 6H), 1.23 (s, 1H), 1.72 (s, 1H),1.96 (s, 1H), 2.10 (s, 3H), 2.33 (m, 1H), 2.88 (m, 1H), 3.01 (m, 3H),3.15 (m, 1H), 3.26 (d, J=13.56 Hz, 2H), 3.60 (m, 1H), 3.76 (d, J=17.97Hz, 1H), 3.91 (m, J=9.49 Hz, 1H), 4.07 (m, 1H), 4.56 (m, 2H), 5.00 (d,J=6.44 Hz, 1H), 6.89 (s, 1H), 6.95 (m, 3H), 7.05 (m, 2H), 7.79 (m, 4H),8.20 (d, J=9.49 Hz, 1H), 8.24 (s, 1H)

Example 387

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=3.73 Hz, 3H), 0.83 (d, J=3.39Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.10 (dd, J=11.02, 6.27 Hz, 1H), 2.71 (dd, J=14.24, 10.51 Hz, 1H), 2.84(dd, J=13.56, 6.78 Hz, 1H), 3.05 (m, 3H), 3.22 (m, 1H), 3.40 (d, J=17.97Hz, 1H), 3.63 (d, J=3.05 Hz, 1H), 3.69 (d, J=17.97 Hz, 1H), 3.81 (d,J=5.43 Hz, 1H), 3.87 (d, J=11.19 Hz, 1H), 4.24 (dd, J=10.00, 5.26 Hz,1H), 4.79 (d, J=15.94 Hz, 1H), 4.87 (d, J=15.94 Hz, 1H), 6.10 (d, J=9.49Hz, 1H), 7.15 (d, J=7.12 Hz, 5H), 7.24 (s, 1H), 7.60 (s, 1H), 7.73 (d,J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H), 8.17 (s, 1H), 8.48 (s, 1H)

Example 388

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (t, J=6.61 Hz, 6H), 0.88 (dd, J=6.78,3.39 Hz, 6H), 3.01 (m, 7H), 2.96 (s, 3H), 3.03 (m, 1H), 3.11 (d, J=3.73Hz, 1H), 3.51 (m, 2H), 3.66 (d, J=17.97 Hz, 1H), 3.97 (s, 2H), 4.23 (s,1H), 4.67 (d, J=7.12 Hz, 1H), 6.51 (s, 1H), 6.83 (s, 1H), 7.09 (s, 1H),7.19 (m, J=32.21 Hz, 5H), 7.73 (d, J=8.48 Hz, 2H), 7.80 (d, J=8.48 Hz,2H), 8.02 (s, 1H), 8.17 (s, 1H)

Example 389

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.77 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 1.25 (m, 1H),2.00 (m, 1H), 2.35 (s, 2H), 2.37 (s, 3H), 2.44 (m, 1H), 2.91 (m, 1H),2.98 (m, 1H), 3.05 (m, 1H), 3.12 (m, 1H), 3.20 (dd, J=13.73, 3.22 Hz,1H), 3.44 (dd, J=14.92, 3.39 Hz, 1H), 3.65 (m, 1H), 3.74 (m, 2H), 4.00(d, J=10.85 Hz, 1H), 4.04 (s, 1H), 4.10 (m, 1H), 4.66 (m, 2H), 6.87 (m,3H), 7.07 (m, 2H), 7.31 (m, 3H), 7.38 (s, 1H), 7.77 (d, J=8.48 Hz, 2H),7.83 (d, J=8.48 Hz, 2H)

Example 390

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.82 (t, J=7.29Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 0.97 (m, 1H),1.24 (t, J=7.12 Hz, 1H), 1.82 (s, 1H), 2.01 (s, 1H), 2.44 (dd, J=13.73,11.70 Hz, 1H), 3.03 (m, 5H), 3.19 (s, 1H), 3.44 (dd, J=14.92, 3.39 Hz,1H), 3.68 (d, J=18.31 Hz, 1H), 3.76 (s, 1H), 4.11 (m, 2H), 4.78 (d,J=5.43 Hz, 2H), 6.90 (m, 3H), 7.10 (m, 2H), 7.63 (t, J=7.80 Hz, 1H),7.78 (d, J=8.48 Hz, 2H), 7.82 (m, 3H), 8.14 (s, 1H), 8.18 (d, J=8.48 Hz,1H), 8.26 (m, 1H)

Example 391

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.78 Hz, 3H), 0.83 (s, 3H),0.87 (m, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.08 (m, 1H), 2.67(dd, J=14.24, 10.51 Hz, 1H), 2.83 (dd, J=13.39, 6.61 Hz, 1H), 3.03 (m,3H), 3.03 (m, 3H), 3.21 (m, 1H), 3.37 (d, J=17.97 Hz, 1H), 3.64 (m, 2H),3.85 (s, 1H), 3.88 (d, J=10.85 Hz, 1H), 4.26 (s, 1H), 5.08 (m, 2H), 6.10(d, J=9.49 Hz, 1H), 7.06 (m, 5H), 7.34 (d, J=4.41 Hz, 1H), 7.64 (m, 1H),7.77 (m, 2H), 8.14 (m, 1H), 8.16 (s, 1H), 8.28 (d, J=7.46 Hz, 1H)

Example 392

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J=6.78 Hz, 3H), 0.80 (m, 9H),0.94 (s, 1H), 1.34 (dd, J=10.34, 3.22 Hz, 1H), 1.80 (s, 1H), 1.97 (m,1H), 2.37 (m, 1H), 3.04 (m, 5H), 3.58 (s, 1H), 3.83 (d, J=17.97 Hz, 1H),4.08 (m, 2H), 4.80 (t, J=16.28 Hz, 2H), 5.01 (d, J=6.78 Hz, 1H), 5.53(s, 2H), 6.78 (d, J=2.37 Hz, 1H), 6.96 (m, 1H), 7.07 (m, 5H), 7.23 (d,J=8.82 Hz, 1H), 7.53 (d, J=9.16 Hz, 1H), 7.79 (m, 4H), 7.93 (d, J=8.48Hz, 1H), 8.24 (s, 1H), 8.25 (d, J=9.49 Hz, 1H)

Example 393

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.83 (d, J=7.12Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 0.97 (d,J=8.48 Hz, 1H), 1.29 (s, 1H), 1.84 (s, 1H), 2.02 (s, 1H), 2.47 (dd,J=13.73, 11.70 Hz, 1H), 2.65 (s, 3H), 3.08 (m, 6H), 3.45 (dd, J=14.75,3.56 Hz, 1H), 3.74 (m, 1H), 3.77 (m, 1H), 4.12 (m, 2H), 4.74 (m, 2H),6.97 (m, 3H), 7.13 (dd, J=6.78, 3.05 Hz, 2H), 7.56 (dd, J=5.09, 1.70 Hz,1H), 7.77 (d, J=8.48 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H), 7.95 (s, 1H),8.14 (s, 1H), 8.65 (d, J=4.75 Hz, 1H)

Example 394

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J=6.78 Hz, 3H), 0.76 (t, J=6.95Hz, 3H), 0.85 (m, 1H), 1.23 (m, 1H), 1.61 (m, 2H), 1.73 (m, 4H), 1.87(m, 2H), 2.10 (s, 3H), 2.38 (dd, J=13.05, 11.36 Hz, 1H), 2.57 (m, 1H),3.11 (m, 6H), 3.51 (s, 1H), 3.77 (d, J=18.31 Hz, 1H), 3.92 (d, J=5.76Hz, 1H), 4.09 (d, J=10.85 Hz, 1H), 4.58 (s, 2H), 5.04 (d, J=6.44 Hz,1H), 6.90 (s, 1H), 6.96 (m, 3H), 7.06 (m, 2H), 7.78 (m, 4H), 8.20 (d,J=9.49 Hz, 1H)

Example 395

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.70 (d, J=6.78 Hz, 3H), 0.76 (d, J=6.44Hz, 3H), 0.90 (m, 1H), 1.69 (m, 4H), 1.95 (m, 2H), 2.39 (m, 1H), 2.57(m, 1H), 3.03 (m, 4H), 3.23 (m, 1H), 3.60 (m, 1H), 3.84 (m, 2H), 3.91(s, 3H), 4.04 (m, 2H), 4.14 (m, 1H), 5.00 (m, 2H), 6.98 (m, 1H), 7.11(dd, J=7.97, 4.24 Hz, 3H), 7.23 (m, 2H), 7.79 (d, J=2.71 Hz, 4H), 7.90(m, 1H), 8.24 (s, 1H), 8.33 (dd, J=4.92, 1.53 Hz, 1H)

Example 396

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (d, J=6.44 Hz, 3H), 0.75 (d, J=6.78Hz, 3H), 1.12 (s, 2H), 1.50 (m, 8H), 1.97 (m, 1H), 2.26 (m, 1H), 2.38(dd, J=12.89, 11.53 Hz, 1H), 3.07 (m, 5H), 3.60 (s, 1H), 3.84 (m, 1H),3.91 (s, 3H), 4.03 (d, J=10.85 Hz, 1H), 5.01 (d, J=6.44 Hz, 3H), 6.98(m, 1H), 7.12 (d, J=4.41 Hz, 3H), 7.22 (m, 2H), 7.78 (m, 4H), 7.90 (dd,J=8.14, 1.36 Hz, 1H), 8.24 (s, 1H), 8.33 (dd, P4.75, 1.36 Hz, 1H)

Example 397

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (m, 3H), 0.86 (m, 6H), 0.92 (d,J=6.44 Hz, 3H), 0.96 (s, 1H), 1.26 (t, J=7.12 Hz, 1H), 1.83 (m, 2H),2.71 (dd, J=14.07, 10.34 Hz, 1H), 2.85 (dd, J=13.56, 6.78 Hz, 1H), 3.04(m, 4H), 3.21 (m, 1H), 3.44 (d, J=17.63 Hz, 1H), 3.67 (d, J=17.97 Hz,1H), 3.75 (s, 1H), 3.83 (s, 1H), 3.99 (d, J=10.85 Hz, 1H), 4.25 (d,J=5.76 Hz, 1H), 4.80 (m, 2H), 6.22 (s, 1H), 7.15 (s, 5H), 7.22 (d,J=7.12 Hz, 1H), 7.64 (m, 1H), 7.72 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48Hz, 2H), 7.85 (m, 1H), 8.16 (s, 1H), 8.52 (d, J=3.73 Hz, 1H)

Example 398

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 6H), 0.87 (d, J=6.44 Hz, 3H),0.92 (d, J=6.44 Hz, 3H), 1.26 (t, J=7.12 Hz, 1H), 1.86 (s, 2H), 2.68 (s,1H), 2.84 (dd, J=13.56, 7.12 Hz, 1H), 3.01 (m, 3H), 3.20 (s, 1H), 3.44(d, P17.97 Hz, 1H), 3.64 (m, 2H), 3.85 (s, 1H), 3.98 (d, J=11.19 Hz,1H), 4.26 (s, 1H), 5.09 (d, P5.09 Hz, 2H), 6.16 (d, J=8.14 Hz, 1H), 7.07(m, 6H), 7.41 (s, 1H), 7.71 (m, J=8.14 Hz, 3H), 7.80 (m, 2H), 7.87 (s,1H), 8.16 (s, 1H), 8.24 (d, J=6.44 Hz, 1H), 8.31 (d, J=8.48 Hz, 1H)

Example 399

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (t, J=7.29 Hz, 6H), 0.95 (m, 1H),1.26 (t, P7.12 Hz, 1H), 1.70 (m, 2H), 1.92 (m, 4H), 2.49 (m, 1H), 2.70(dd, J=14.24, 10.51 Hz, 1H), 3.07 (m, 4H), 3.25 (m, 1H), 3.44 (d,J=17.97 Hz, 1H), 3.50 (d, J=2.37 Hz, 1H), 3.64 (d, J=17.97 Hz, 1H), 3.82(s, 1H), 4.00 (d, J=11.19 Hz, 1H), 4.28 (s, 1H), 5.09 (d, J=4.41 Hz,2H), 6.22 (d, J=9.49 Hz, 1H), 7.06 (m, 5H), 7.38 (d, J=3.73 Hz, 1H),7.65 (d, J=7.12 Hz, 1H), 7.71 (d, J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz,2H), 7.99 (s, 1H), 8.16 (s, 1H), 8.20 (d, J=8.48 Hz, 1H), 8.29 (d,J=8.48 Hz, 1H), 8.89 (d, J=4.07 Hz, 1H)

Example 400

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.44 Hz, 3H), 0.83 (m, 3H),0.96 (m, 1H), 1.23 (m, 2H), 1.58 (m, 8H), 1.93 (m, 1H), 2.10 (m, 1H),2.69 (dd, J=14.41, 10.68 Hz, 1H), 3.07 (m, 3H), 3.43 (d, J=17.97 Hz,1H), 3.63 (m, 2H), 3.89 (m, 1H), 3.99 (d, J=11.19 Hz, 1H), 4.27 (m, 1H),5.08 (m, 2H), 6.19 (d, P9.49 Hz, 1H), 7.06 (m, 5H), 7.36 (d, J=4.41 Hz,1H), 7.65 (m, 2H), 7.72 (m, 2H), 7.77 (d, P8.48 Hz, 2H), 8.17 (m, 1H),8.16 (s, 1H), 8.29 (d, J=8.48 Hz, 1H), 8.88 (d, J=4.41 Hz, 1H)

Example 401

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, P6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (dd,J=8.31, 6.61 Hz, 1H), 2.06 (m, 1H), 2.63 (dd, J=14.07, 10.68 Hz, 1H),2.84 (dd, J=13.56, 6.78 Hz, 1H), 3.03 (m, 4H), 3.22 (m, 2H), 3.55 (d,J=17.63 Hz, 1H), 3.67 (s, 1H), 3.82 (d, J=2.71 Hz, 1H), 3.86 (d, J=10.85Hz, 1H), 4.19 (m, 1H), 4.49 (d, J=14.24 Hz, 1H), 4.52 (d, J=14.24 Hz,1H), 6.14 (d, J=9.16 Hz, 1H), 6.60 (dd, J=7.63, 1.86 Hz, 1H), 6.76 (s,1H), 6.80 (d, J=7.80 Hz, 1H), 7.04 (m, 5H), 7.10 (m, 1H), 7.72 (d,J=8.48 Hz, 2H), 7.79 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 402

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (m, 6H), 0.87 (d, J=6.44 Hz, 3H),0.90 (d, J=6.44 Hz, 3H), 2.01 (m, 1H), 2.21 (s, 3H), 2.41 (dd, J=13.56,11.87 Hz, 1H), 3.06 (m, 7H), 3.44 (m, 1H), 3.65 (d, J=17.97 Hz, 1H),3.75 (m, 1H), 4.00 (d, J=11.19 Hz, 1H), 4.11 (m, 1H), 4.67 (s, 2H), 6.85(m, 3H), 7.06 (m, 2H), 7.39 (m, 2H), 7.59 (m, 1H), 7.72 (s, 1H), 7.77(d, J=8.82 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H), 8.14 (s, 1H)

Example 403

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.78 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 1.29 (s, 2H),2.02 (m, 2H), 2.44 (dd, J=13.56, 11.87 Hz, 1H), 2.98 (m, 3H), 3.11 (m,1H), 3.20 (m, 1H), 3.44 (m, 1H), 3.67 (m, 1H), 3.76 (m, 1H), 3.86 (d,J=4.07 Hz, 2H), 4.00 (d, J=10.85 Hz, 1H), 4.12 (m, 1H), 4.66 (m, 1H),4.79 (s, 2H), 6.89 (m, 3H), 7.08 (m, 2H), 7.32 (m, 3H), 7.40 (s, 1H),7.77 (d, J=8.82 Hz, 2H), 7.83 (d, J=8.48 Hz, 2H), 8.14 (s, 1H)

Example 404

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.82 (t, J=7.29Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.24 (m, 2H),1.80 (s, 1H), 2.01 (m, 1H), 2.41 (dd, J=13.73, 11.70 Hz, 1H), 0.00(none, 3H), 3.11 (m, 1H), 3.20 (dd, J=13.56, 3.39 Hz, 2H), 3.44 (dd,J=14.75, 3.56 Hz, 1H), 3.60 (d, J=17.97 Hz, 1H), 3.75 (m, 1H), 4.11 (m,2H), 4.53 (s, 2H), 6.64 (m, 1H), 6.64 (m, 1H), 6.71 (d, J=7.46 Hz, 1H),6.71 (d, J=7.46 Hz, 1H), 6.77 (d, J=1.70 Hz, 1H), 6.77 (d, J=1.70 Hz,1H), 6.90 (m, 5H), 6.90 (m, 3H), 7.07 (m, 4H), 7.83 (d, J=8.48 Hz, 2H),8.14 (s, 1H)

Example 405

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.82 (t, J=7.46Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.27 (dd,J=13.90, 4.41 Hz, 1H), 1.83 (s, 1H), 2.01 (m, 1H), 2.25 (s, 3H), 2.46(dd, J=13.73, 11.70 Hz, 1H), 3.03 (m, 6H), 3.21 (dd, J=13.56, 3.39 Hz,1H), 3.45 (dd, J=14.75, 3.56 Hz, 1H), 3.71 (d, J=17.97 Hz, 1H), 3.77 (m,1H), 4.13 (m, 2H), 4.70 (d, J=7.80 Hz, 2H), 6.94 (m, 3H), 7.11 (m, 2H),7.32 (dd, J=5.09, 1.70 Hz, 1H), 7.80 (q, J=8.48 Hz, 4H), 7.85 (d, J=3.73Hz, 1H), 8.14 (s, 1H), 8.51 (d, J=5.09 Hz, 1H)

Example 436

¹H NMR (300 MHz, CDCl₃) δ ppm 0.85 (m, 12H), 1.91 (m, 1H), 2.22 (s, 1H),2.95 (m, 7H), 2.98 (s, 3H), 3.36 (dd, J=15.26, 4.41 Hz, 1H), 3.85 (s,1H), 4.11 (m, 1H), 4.22 (s, 1H), 4.31 (d, J=15.94 Hz, 1H), 7.18 (m, 5H),7.29 (s, 1H), 7.70 (d, J=8.48 Hz, 2H), 7.76 (s, 1H), 7.82 (d, J=8.48 Hz,2H), 8.13 (s, 1H), 8.29 (s, 1H), 8.51 (s, 1H)

Example 437

¹H NMR (300 MHz, CDCl₃) δ ppm 0.68 (d, J=6.78 Hz, 3H), 0.87 (m, 9H),1.89 (dd, J=13.73, 6.95 Hz, 1H), 2.23 (m, 1H), 2.68 (s, 3H), 2.85 (dd,J=13.39, 7.29 Hz, 1H), 2.93 (s, 3H), 3.02 (m, 4H), 3.35 (dd, J=15.09,4.58 Hz, 1H), 3.85 (m, 1H), 4.10 (d, J=4.75 Hz, 1H), 4.21 (d, J=15.94Hz, 2H), 4.53 (d, J=15.94 Hz, 1H), 6.16 (s, 1H), 6.76 (s, 1H), 6.96 (s,1H), 7.18 (m, 5H), 7.71 (d, J=8.48 Hz, 2H), 7.82 (d, J=8.48 Hz, 2H),8.13 (s, 1H)

Example 438

¹H NMR (300 MHz, CDCl₃) δ ppm 0.67 (d, J=6.78 Hz, 3H), 0.87 (m, 9H),1.69 (s, 1H), 1.89 (m, 1H), 2.20 (s, 1H), 2.86 (dd, J=13.56, 7.46 Hz,1H), 2.94 (s, 3H), 3.02 (m, 3H), 3.33 (dd, J=15.26, 4.75 Hz, 1H), 3.50(s, 3H), 3.85 (m, 1H), 4.09 (s, 1H), 4.22 (s, 1H), 4.28 (d, J=16.28 Hz,1H), 4.56 (d, J=16.62 Hz, 1H), 4.68 (s, 2H), 6.77 (s, 1H), 7.11 (s, 1H),7.20 (m, 5H), 7.71 (d, J=8.48 Hz, 2H), 7.82 (d, J=8.48 Hz, 2H), 8.13 (s,1H)

Example 439

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.99 (t, J=6.95 Hz, 3H), 1.08 (d, J=7.12 Hz, 3H), 1.29 (d,J=6.78 Hz, 6H), 1.96 (m, 1H), 2.57 (dd, J=13.90, 10.51 Hz, 1H), 2.85 (m,2H), 3.02 (m, 2H), 3.26 (m, 6H), 3.78 (m, 2H), 4.10 (m, 1H), 6.38 (s,1H), 7.12 (m, 5H), 7.22 (s, 1H), 7.62 (d, J=8.82 Hz, 1H), 7.76 (d,J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 440

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=3.39 Hz, 3H), 0.78 (d, J=3.39Hz, 3H), 1.13 (m, 2H), 1.26 (m, 2H), 1.37 (d, J=6.78 Hz, 6H), 1.59 (m,8H), 1.90 (m, 1H), 2.23 (dd, J=15.09, 7.63 Hz, 1H), 2.65 (dd, J=13.90,10.51 Hz, 1H), 2.94 (s, 3H), 3.07 (m, 2H), 3.21 (m, 1H), 3.46 (dd,J=14.92, 3.73 Hz, 1H), 3.82 (m, 1H), 3.96 (d, J=7.46 Hz, 1H), 4.10 (m,1H), 4.48 (m, 2H), 7.15 (m, 6H), 7.76 (d, J=8.82 Hz, 2H), 7.81 (d,J=8.82 Hz, 2H), 8.13 (s, 1H)

Example 441

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=3.05 Hz, 3H), 0.78 (d, J=3.05Hz, 3H), 1.36 (d, J=6.78 Hz, 6H), 1.66 (m, 2H), 1.78 (m, 2H), 1.96 (m,4H), 2.58 (dd, J=14.92, 7.46 Hz, 1H), 2.65 (m, 1H), 2.94 (s, 3H), 3.11(m, 6H), 3.42 (dd, J=14.75, 3.90 Hz, 1H), 3.78 (m, 1H), 3.95 (d, J=7.46Hz, 1H), 4.08 (m, 1H), 4.48 (m, 2H), 7.15 (m, 6H), 7.77 (d, J=8.82 Hz,2H), 7.82 (d, J=8.48 Hz, 2H), 8.14 (s, 1H)

Example 442

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.78 (t, J=7.46Hz, 3H), 0.97 (m, 1H), 1.14 (d, J=6.10 Hz, 1H), 1.24 (m, 2H), 1.61 (m,8H), 2.24 (m, 1H), 2.66 (dd, J=14.07, 10.68 Hz, 1H), 2.94 (s, 3H), 3.12(m, 5H), 3.47 (dd, J=14.92, 3.73 Hz, 1H), 3.83 (m, 1H), 4.01 (d, J=7.46Hz, 1H), 4.13 (m, 1H), 4.55 (s, 2H), 7.16 (m, 5H), 7.31 (t, J=7.46 Hz,2H), 7.77 (m, 3H), 7.82 (d, J=6.44 Hz, 2H), 8.13 (s, 1H), 8.48 (d,J=4.07 Hz, 1H)

Example 443

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.78 (m, 3H),0.98 (m, 1H), 1.24 (m, 1H), 1.73 (m, 5H), 1.96 (m, 2H), 2.57 (dd,J=15.26, 7.46 Hz, 1H), 2.66 (m, 2H), 2.94 (s, 3H), 3.02 (dd, J=14.75,8.65 Hz, 1H), 3.17 (m, 2H), 3.43 (m, 1H), 3.79 (m, 1H), 4.01 (m, 2H),4.12 (m, 1H), 4.55 (s, 2H), 6.23 (d, J=7.80 Hz, 1H), 7.16 (m, 5H), 7.31(m, J=7.12, 7.12 Hz, 2H), 7.78 (m, 3H), 7.83 (d, J=8.82 Hz, 2H), 8.13(s, 1H), 8.48 (d, J=4.41 Hz, 1H)

Example 444

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.44 Hz, 3H), 1.03 (s, 9H),1.08 (m, 1H), 1.57 (d, J=28.14 Hz, 1H), 1.71 (m, 1H), 1.76 (s, 1H), 1.84(d, J=20.35 Hz, 1H), 2.54 (m, 1H), 2.67 (dd, J=13.73, 9.66 Hz, 1H), 2.87(s, 3H), 2.97 (m, 1H), 3.08 (m, 1H), 3.25 (d, J=7.80 Hz, 1H), 3.35 (d,J=4.07 Hz, 1H), 3.38 (s, 3H), 3.61 (s, 1H), 3.81 (m, 1H), 3.93 (dd,J=6.44, 4.41 Hz, 1H), 4.00 (s, 1H), 4.47 (d, J=4.41 Hz, 2H), 4.65 (s,2H), 5.05 (d, J=6.44 Hz, 1H), 5.80 (d, J=6.78 Hz, 1H), 7.15 (m, 1H),7.22 (m, 5H), 7.37 (s, 1H), 7.40 (d, J=9.16 Hz, 1H), 7.77 (d, J=8.48 Hz,2H), 7.81 (d, J=8.82 Hz, 2H), 8.24 (s, 1H)

Example 445

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.84 (d, J=6.44 Hz, 3H), 1.03 (s, 9H),1.08 (m, 2H), 1.19 (m, 2H), 1.50 (s, 6H), 2.19 (s, 1H), 2.87 (s, 3H),2.96 (m, 2H), 3.14 (dd, J=14.07, 8.65 Hz, 1H), 3.38 (s, 3H), 3.65(0=10.85 Hz, 1H), 3.81 (dd, J=6.10, 4.41 Hz, 1H), 3.94 (dd, J=6.61, 4.58Hz, 1H), 4.03 (s, 1H), 4.47 (d, J=4.41 Hz, 2H), 4.65 (s, 2H), 5.02 (d,J=6.44 Hz, 1H), 5.80 (d, J=6.78 Hz, 1H), 7.16 (m, 1H), 7.20 (d, J=8.14Hz, 5H), 7.23 (s, 1H), 7.38 (m, 1H), 7.76 (d, J=8.48 Hz, 2H), 7.81 (d,J=8.48 Hz, 2H)

Example 446

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.59 (d, J=6.44 Hz, 3H), 0.70 (t, J=7.29Hz, 3H), 1.27 (m, 2H), 1.56 (m, 3H), 1.74 (m, 2H), 1.86 (m, 2H), 2.57(m, 1H), 2.85 (s, 3H), 2.92 (m, 1H), 3.01 (m, 1H), 3.07 (m, 1H), 3.26(m, 1H), 3.38 (s, 3H), 3.60 (m, J=4.41 Hz, 1H), 3.94 (t, J=7.97 Hz, 2H),4.41 (d, J=15.94 Hz, 1H), 4.51 (d, J=16.28 Hz, 1H), 4.64 (s, 2H), 5.02(d, J=6.10 Hz, 1H), 5.98 (d, J=8.48 Hz, 1H), 7.14 (m, 5H), 7.32 (s, 1H),7.67 (d, J=8.82 Hz, 1H), 7.79 (t, J=8.82 Hz, 4H)

Example 447

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.59 (d, J=6.78 Hz, 3H), 0.70 (t, J=7.46Hz, 3H), 0.88 (m, 1H), 1.07 (m, 1H), 1.24 (m, 2H), 1.52 (m, 8H), 2.57(m, 1H), 2.84 (s, 3H), 2.98 (m, 2H), 3.13 (m, 1H), 3.28 (s, 1H), 3.38(s, 3H), 3.61 (s, 1H), 3.95 (t, J=8.14 Hz, 2H), 4.41 (d, J=16.28 Hz,1H), 4.50 (d, J=16.28 Hz, 1H), 4.64 (s, 2H), 4.99 (d, J=6.10 Hz, 1H),5.97 (d, J=8.14 Hz, 1H), 7.14 (m, 5H), 7.31 (s, 1H), 7.69 (d, J=9.16 Hz,1H), 7.76 (d, J=8.82 Hz, 2H), 7.78 (d, J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 448

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.78, 1.70 Hz, 6H), 0.98 (m,1H), 1.64 (m, 2H), 1.80 (m, 2H), 1.96 (m, 4H), 2.59 (m, 2H), 2.67 (s,3H), 2.70 (m, 1H), 2.93 (s, 3H), 2.99 (m, 1H), 3.17 (m, 2H), 3.43 (dd,J=14.75, 3.90 Hz, 1H), 3.78 (m, 1H), 3.96 (d, J=7.12 Hz, 1H), 4.10 (m,1H), 4.43 (d, J=15.94 Hz, 1H), 4.52 (d, J=16.28 Hz, 1H), 7.16 (m, 6H),7.77 (d, J=8.48 Hz, 2H), 7.82 (d, J=8.82 Hz, 2H), 8.14 (s, 1H)

Example 449

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.59 (d, J=6.78 Hz, 3H), 0.69 (t, J=7.46Hz, 3H), 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44 Hz, 3H), 0.93 (m, 1H),1.19 (m, 1H), 1.59 (s, 1H), 1.96 (m, 1H), 2.60 (s, 3H), 2.83 (s, 3H),2.90 (m, 1H), 2.98 (m, 1H), 3.03 (m, 1H), 3.31 (m, 2H), 3.59 (s, 1H),3.95 (m, 2H), 4.35 (d, J=16.28 Hz, 1H), 4.47 (d, J=15.94 Hz, 1H), 4.97(d, J=6.44 Hz, 1H), 6.02 (d, J=8.48 Hz, 1H), 7.14 (m, 6H), 7.67 (d,J=9.16 Hz, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H), 8.23(s, 1H)

Example 450

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (t, J=7.29 Hz, 3H), 0.84 (d, J=7.12Hz, 3H), 0.96 (m, 1H), 1.66 (m, 2H), 1.83 (m, 3H), 1.98 (m, 4H), 2.52(dd, J=14.92, 7.46 Hz, 1H), 2.65 (s, 3H), 2.91 (s, 3H), 3.03 (m, 2H),3.25 (m, 1H), 3.41 (dd, J=14.75, 5.93 Hz, 1H), 3.82 (m, 1H), 4.17 (d,J=16.28 Hz, 1H), 4.24 (m, 3H), 4.53 (d, J=16.28 Hz, 1H), 6.23 (s, 1H),6.82 (d, J=8.14 Hz, 1H), 6.95 (s, 1H), 7.19 (m, 5H), 7.73 (d, J=8.48 Hz,2H), 7.85 (d, J=8.48 Hz, 2H), 8.14 (s, 1H)

Example 451

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.83 (dd,J=8.14, 6.44 Hz, 6H), 1.02 (s, 9H), 1.95 (m, 1H), 2.62 (s, 3H), 2.68(dd, J=13.90, 9.49 Hz, 1H), 2.86 (s, 3H), 2.93 (m, 4H), 3.62 (s, 1H),3.79 (dd, J=10.85, 6.44 Hz, 1H), 3.94 (dd, J=6.61, 4.58 Hz, 1H), 4.03(m, 1H), 4.42 (t, J=16.62 Hz, 2H), 5.01 (d, J=6.44 Hz, 1H), 5.84 (d,J=6.44 Hz, 1H), 7.16 (m, 5H), 7.22 (s, 1H), 7.36 (d, J=9.49 Hz, 1H),7.76 (d, J=8.82 Hz, 2H), 7.80 (d, J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 452

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.85 (d, J=6.10 Hz, 3H), 1.03 (s, 9H),1.57 (d, J=27.13 Hz, 2H), 1.71 (m, 3H), 1.87 (s, 2H), 2.62 (s, 3H), 2.68(dd, J=13.90, 9.83 Hz, 1H), 2.86 (s, 3H), 2.95 (m, 2H), 3.08 (m, 1H),3.26 (m, 1H), 3.61 (s, 1H), 3.81 (dd, J=6.10, 4.41 Hz, 1H), 3.93 (dd,J=6.44, 4.41 Hz, 2H), 4.38 (d, J=16.28 Hz, 1H), 4.42 (d, J=16.28 Hz,2H), 5.05 (d, J=6.10 Hz, 1H), 5.85 (d, J=6.44 Hz, 1H), 7.17 (m, 5H),7.23 (s, 1H), 7.38 (d, J=9.16 Hz, 1H), 7.77 (d, J=8.82 Hz, 2H), 7.81 (d,J=8.48 Hz, 2H), 8.23 (s, 1H)

Example 453

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (t, J=6.44 Hz, 6H), 0.87 (d, J=6.78Hz, 6H), 1.16 (m, 1H), 1.52 (s, 1H), 1.88 (m, 1H), 2.88 (s, 3H), 2.94(d, J=11.19 Hz, 1H), 3.07 (m, 2H), 3.07 (m, 2H), 3.21 (m, 1H), 3.87 (m,1H), 3.99 (d, J=3.73 Hz, 1H), 4.13 (dd, J=7.63, 5.93 Hz, 1H), 4.23 (m,1H), 4.45 (d, J=15.94 Hz, 1H), 4.67 (m, 2H), 6.43 (d, J=8.14 Hz, 1H),7.21 (m, 5H), 7.51 (m, 2H), 7.70 (d, J=6.44 Hz, 2H), 7.71 (s, 1H), 7.79(d, J=8.48 Hz, 2H), 8.05 (s, 1H), 8.14 (s, 1H)

Example 454

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.78 (t, J=7.46Hz, 3H), 0.85 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 0.97 (m, 1H),1.28 (m, 1H), 1.64 (s, 1H), 2.00 (m, 1H), 2.61 (dd, J=13.90, 10.85 Hz,1H), 2.94 (s, 3H), 3.07 (m, 7H), 3.46 (dd, J=14.92, 3.73 Hz, 1H), 3.83(s, 3H), 3.96 (d, J=8.14 Hz, 1H), 4.09 (m, 1H), 4.23 (d, J=16.28 Hz,1H), 4.38 (d, J=16.28 Hz, 1H), 6.81 (s, 1H), 7.09 (m, 5H), 7.80 (q,J=8.48 Hz, 4H), 7.87 (m, 1H), 8.13 (s, 1H)

Example 455

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (dd, J=9.16, 6.78 Hz, 6H), 1.57(dd, J=16.62, 8.82 Hz, 2H), 1.71 (m, 2H), 1.84 (dd, J=13.73, 6.61 Hz,4H), 2.56 (m, J=20.01 Hz, 1H), 2.85 (s, 3H), 2.91 (m, 1H), 3.00 (m, 1H),3.07 (m, 1H), 3.26 (d, J=9.83 Hz, 2H), 3.37 (s, 3H), 3.60 (d, J=3.05 Hz,1H), 3.90 (m, 2H), 4.42 (d, J=16.28 Hz, 1H), 4.51 (d, J=16.28 Hz, 1H),4.64 (s, 2H), 5.03 (d, J=6.44 Hz, 1H), 5.96 (d, J=8.48 Hz, 1H), 7.14 (m,5H), 7.32 (s, 1H), 7.70 (d, J=9.49 Hz, 1H), 7.78 (m, 4H), 8.23 (s, 1H)

Example 456

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (t, J=7.29 Hz, 3H), 0.80 (d, J=7.12Hz, 3H), 0.93 (m, 1H), 1.29 (s, 1H), 1.66 (dd, J=16.62, 9.16 Hz, 2H),1.81 (m, 2H), 1.97 (m, 2H), 2.61 (m, 1H), 2.86 (s, 3H), 2.99 (d, J=2.03Hz, 3H), 3.03 (m, 1H), 3.12 (m, 3H), 3.16 (m, 2H), 3.44 (dd, J=14.58,4.07 Hz, 1H), 3.80 (m, 1H), 3.98 (m, 1H), 4.10 (s, 1H), 4.28 (d, J=15.94Hz, 1H), 4.36 (d, J=15.94 Hz, 1H), 6.16 (s, 1H), 6.84 (s, 1H), 7.06 (m,3H), 7.18 (m, 2H), 7.80 (q, J=8.59 Hz, 4H), 7.87 (d, J=9.16 Hz, 1H),8.14 (s, 1H)

Example 457

¹H NMR (300 MHz, CD₃OD) δ ppm 0.69 (d, J=6.44 Hz, 3H), 0.80 (t, J=7.29Hz, 3H), 0.85 (d, J=6.78 Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.99 (m, 1H),1.35 (m, 1H), 1.64 (m, 1H), 2.00 (m, 1H), 2.63 (dd, J=13.90, 10.85 Hz,1H), 2.86 (s, 3H), 2.95 (m, 1H), 3.06 (m, 2H), 3.15 (m, 2H), 3.28 (s,1H), 3.46 (dd, J=14.92, 3.39 Hz, 1H), 3.79 (m, 1H), 4.00 (d, J=8.48 Hz,1H), 4.09 (m, 1H), 4.45 (d, J=15.94 Hz, 1H), 4.62 (d, J=15.94 Hz, 1H),7.15 (m, 5H), 7.39 (dd, J=7.46, 4.41 Hz, 1H), 7.70 (m, 1H), 7.79 (q,J=8.82 Hz, 4H), 8.13 (s, 1H), 8.43 (dd, J=4.92, 1.53 Hz, 2H)

Example 458

¹H NMR (300 MHz, CD₃OD) δ ppm 0.70 (d, J=6.44 Hz, 3H), 0.80 (t, J=7.29Hz, 3H), 1.00 (m, 1H), 1.35 (m, 1H), 1.66 (m, 2H), 1.80 (m, 3H), 1.95(m, 3H), 1.95 (m, 2H), 2.62 (m, 2H), 2.91 (s, 3H), 3.00 (dd, J=14.75,8.65 Hz, 1H), 3.17 (m, 1H), 3.27 (s, 2H), 3.45 (dd, J=14.58, 4.07 Hz,1H), 3.79 (m, 1H), 4.00 (d, J=8.48 Hz, 1H), 4.10 (m, 1H), 4.47 (d,J=16.95 Hz, 1H), 4.62 (d, J=17.29 Hz, 1H), 7.17 (m, 7H), 7.76 (d, J=8.82Hz, 2H), 7.79 (d, J=6.78 Hz, 2H), 8.13 (s, 1H), 8.44 (m, 1H)

Example 459

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (dd, J=14.92, 6.78 Hz, 6H), 0.87 (m,6H), 2.93 (s, 3H), 2.89 (m, 8H), 3.33 (s, 1H), 3.50 (s, 3H), 3.85 (s,2H), 4.21 (m, 3H), 4.57 (d, J=15.94 Hz, 1H), 4.67 (s, 2H), 6.68 (d,J=8.82 Hz, 1H), 7.11 (s, 1H), 7.20 (dd, J=18.31, 8.14 Hz, 5H), 7.55 (d,J=8.82 Hz, 1H), 7.71 (d, J=8.14 Hz, 2H), 7.82 (d, J=8.48 Hz, 2H), 8.14(s, 1H)

Example 460

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.79 (t, J=7.46Hz, 3H), 0.99 (m, 1H), 1.14 (m, 1H), 1.30 (m, 2H), 1.60 (m, 8H), 2.24(m, 1H), 2.65 (dd, J=13.90, 10.51 Hz, 1H), 2.95 (s, 3H), 3.12 (m, 5H),3.44 (m, 3H), 3.46 (m, 1H), 3.82 (m, 1H), 4.00 (d, J=8.14 Hz, 1H), 4.11(m, 1H), 4.45 (d, J=16.28 Hz, 1H), 4.50 (s, 2H), 4.55 (d, J=16.28 Hz,1H), 7.11 (m, 5H), 7.19 (m, 2H), 7.37 (d, J=7.80 Hz, 1H), 7.76 (d,J=7.12 Hz, 2H), 7.82 (d, J=8.82 Hz, 2H), 8.13 (s, 1H)

Example 461

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.59 (d, J=6.78 Hz, 3H), 0.69 (t, J=7.46Hz, 3H), 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44 Hz, 3H), 0.92 (m, 1H),1.22 (m, 1H), 1.30 (d, J=6.78 Hz, 6H), 1.59 (s, 1H), 1.94 (m, 1H), 2.56(m, 1H), 2.85 (s, 3H), 2.96 (m, 4H), 3.21 (dd, J=13.90, 6.78 Hz, 1H),3.61 (m, 1H), 3.94 (t, J=7.97 Hz, 2H), 4.37 (d, J=16.28 Hz, 1H), 4.47(d, J=16.28 Hz, 1H), 4.97 (d, J=6.44 Hz, 1H), 5.98 (d, J=8.82 Hz, 1H),7.14 (m, 6H), 7.69 (d, J=9.16 Hz, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.80 (d,J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 462

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.60 (d, J=6.78 Hz, 3H), 0.69 (t, J=7.29Hz, 3H), 0.91 (m, 1H), 1.07 (m, 1H), 1.20 (m, 3H), 1.30 (d, J=6.78 Hz,6H), 1.48 (dd, J=17.80, 7.29 Hz, 8H), 2.19 (m, 1H), 2.57 (m, 1H), 2.85(s, 3H), 2.97 (m, 1H), 3.14 (m, 1H), 3.36 (m, J=3.73 Hz, 1H), 3.59 (s,1H), 3.95 (m, J=7.97, 7.97 Hz, 2H), 4.37 (d, J=16.28 Hz, 1H), 4.46 (d,J=16.28 Hz, 1H), 4.98 (d, J=6.44 Hz, 1H), 5.98 (d, J=8.48 Hz, 1H), 7.13(m, 6H), 7.69 (d, J=8.82 Hz, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.80 (d,J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 463

¹H NMR (300 MHz, CD₃OD) δ ppm 0.69 (d, J=6.78 Hz, 3H), 0.75 (t, J=7.46Hz, 3H), 0.91 (m, 1H), 1.14 (m, 1H), 1.29 (m, 2H), 1.60 (m, 8H), 2.23(dd, J=14.92, 7.46 Hz, 1H), 2.64 (dd, J=13.90, 10.85 Hz, 1H), 2.99 (s,3H), 3.12 (m, 6H), 3.46 (dd, J=14.58, 3.73 Hz, 1H), 3.82 (m, 1H), 3.98(d, J=8.14 Hz, 1H), 4.10 (m, 1H), 4.46 (d, J=16.28 Hz, 1H), 4.60 (d,J=16.62 Hz, 1H), 4.79 (s, 2H), 7.14 (m, 6H), 7.29 (dd, J=6.78, 2.03 Hz,1H), 7.76 (m, 3H), 7.82 (d, J=8.82 Hz, 2H), 8.13 (s, 1H)

Example 464

¹H NMR (300 MHz, CD₃OD) δ ppm 0.86 (s, 9H), 1.19 (m, 3H), 1.62 (m, 8H),2.23 (m, 1H), 2.61 (dd, J=13.73, 10.68 Hz, 1H), 2.96 (s, 3H), 3.08 (m,2H), 3.20 (m, 1H), 3.43 (s, 3H), 3.47 (m, 1H), 3.82 (m, 1H), 4.03 (s,1H), 4.11 (m, 1H), 4.38 (d, J=16.28 Hz, 1H), 4.49 (s, 2H), 4.58 (d,J=16.28 Hz, 1H), 7.00 (m, 1H), 7.13 (m, 5H), 7.37 (d, J=7.80 Hz, 1H),7.77 (m, 3H), 7.81 (d, J=2.37 Hz, 2H), 8.13 (s, 1H)

Example 465

¹H NMR (300 MHz, CDCl₃) δ ppm 0.91 (s, 9H), 1.19 (m, 3H), 1.27 (m, 2H),1.29 (s, 9H), 1.55 (m, 8H), 2.12 (m, 1H), 2.87 (m, 1H), 3.02 (d, J=7.72Hz, 2H), 3.08 (m, 1H), 3.25 (m, 1H), 3.88 (m, 1H), 3.94 (d, J=7.72 Hz,1H), 4.12 (m, 1H), 4.33 (d, J=15.81 Hz, 1H), 4.44 (d, J=15.81 Hz, 1H),4.52 (s, 2H), 6.42 (d, J=8.09 Hz, 1H), 7.11 (m, 6H), 7.47 (d, J=7.72 Hz,1H), 7.69 (m, 3H), 7.78 (d, J=8.46 Hz, 2H), 8.14 (s, 1H)

Example 466

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.87 (d, J=6.10 Hz, 3H), 1.55 (d,J=27.80 Hz, 2H), 1.70 (d, J=14.92 Hz, 3H), 1.86 (s, 2H), 2.62 (m, 1H),2.84 (d, J=3.39 Hz, 2H), 2.86 (s, 3H), 2.94 (d, J=3.39 Hz, 1H), 2.99 (d,J=10.17 Hz, 1H), 3.07 (dd, J=14.07, 6.95 Hz, 1H), 3.25 (m, 1H), 3.37 (d,J=3.39 Hz, 3H), 3.59 (s, 1H), 3.82 (m, 1H), 3.89 (s, 1H), 3.96 (dd,J=7.46, 5.09 Hz, 1H), 4.48 (s, 2H), 4.65 (s, 2H), 5.98 (d, J=7.80 Hz,1H), 7.17 (m, 5H), 7.32 (s, 1H), 7.61 (d, J=9.16 Hz, 1H), 7.76 (d,J=8.48 Hz, 2H), 7.82 (d, J=8.82 Hz, 2H), 8.23 (s, 1H)

Example 467

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.87 (d, J=6.10 Hz, 3H), 1.06 (d,J=20.01 Hz, 2H), 1.25 (s, 1H), 1.44 (d, J=32.89 Hz, 8H), 2.20 (d, J=7.80Hz, 1H), 2.60 (dd, J=13.90, 10.17 Hz, 1H), 2.86 (s, 3H), 2.97 (m, 5H),3.11 (m, 1H), 3.62 (s, 1H), 3.82 (m, 1H), 3.89 (s, 1H), 3.97 (dd,J=7.46, 5.43 Hz, 1H), 4.48 (s, 2H), 4.65 (s, 2H), 5.97 (d, J=7.46 Hz,1H), 7.16 (m, 5H), 7.32 (s, 1H), 7.62 (d, J=9.16 Hz, 1H), 7.75 (d,J=8.48 Hz, 2H), 7.81 (d, J=8.82 Hz, 2H), 8.22 (s, 1H)

Example 468

¹H NMR (300 MHz, CD₃OD) δ ppm 0.65 (d, J=6.78 Hz, 3H), 0.74 (t, J=7.29Hz, 3H), 0.84 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.20 (m, 1H),1.59 (s, 1H), 2.00 (m, 1H), 2.61 (dd, J=14.07, 10.68 Hz, 1H), 2.88 (s,3H), 3.05 (m, 4H), 3.45 (dd, J=14.75, 3.56 Hz, 1H), 3.81 (m, 1H), 4.00(d, J=7.46 Hz, 1H), 4.08 (m, 1H), 4.31 (d, J=16.28 Hz, 1H), 4.44 (d,J=15.94 Hz, 1H), 4.79 (s, 3H), 6.54 (d, J=7.46 Hz, 1H), 6.61 (m, 2H),7.06 (t, J=7.63 Hz, 1H), 7.16 (m, 5H), 7.77 (d, J=8.48 Hz, 2H), 7.83 (d,J=8.82 Hz, 2H), 8.13 (s, 1H)

Example 469

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.80 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 1.93 (s, 1H), 2.61 (s, 3H), 2.85 (s,3H), 2.99 (m, 1H), 3.38 (m, 1H), 3.54 (s, 5H), 3.81 (m, 2H), 3.97 (m,1H), 4.44 (s, 2H), 6.00 (d, J=6.78 Hz, 1H), 7.14 (s, 1H), 7.15 (m, 5H),7.61 (d, J=9.16 Hz, 1H), 7.76 (d, J=8.48 Hz, 2H), 7.81 (d, J=8.48 Hz,2H), 8.23 (s, 1H)

Example 470

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.88 (d, J=6.44 Hz, 3H), 1.55 (d,J=27.47 Hz, 2H), 1.70 (m, 3H), 1.86 (s, 2H), 2.61 (s, 3H), 2.85 (s, 3H),2.94 (m, 1H), 3.06 (m, 2H), 3.27 (m, 5H), 3.85 (m, 3H), 4.44 (s, 2H),6.01 (d, J=6.78 Hz, 1H), 7.15 (s, 1H), 7.17 (m, 5H), 7.60 (d, J=9.16 Hz,1H), 7.76 (d, J=8.48 Hz, 2H), 7.82 (d, J=8.48 Hz, 2H), 8.23 (s, 1H)

Example 471

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=6.44 Hz, 3H), 0.73 (t, J=7.46Hz, 3H), 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44 Hz, 3H), 0.96 (m, 1H),1.38 (s, 1H), 1.60 (s, 1H), 1.96 (m, 1H), 2.55 (m, 1H), 2.82 (d, J=6.78Hz, 1H), 2.88 (s, 3H), 2.98 (m, 2H), 3.34 (m, 1H), 3.62 (s, 2H), 3.91(s, 1H), 4.01 (m, 1H), 4.40 (d, J=16.28 Hz, 3H), 4.55 (d, J=15.94 Hz,1H), 6.14 (d, J=8.48 Hz, 1H), 7.09 (m, 5H), 7.42 (s, 1H), 7.78 (m, 4H),7.94 (d, J=9.16 Hz, 1H), 8.24 (s, 1H), 8.42 (s, 2H)

Example 472

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J=6.44 Hz, 3H), 0.74 (t, J=7.46Hz, 3H), 0.95 (m, J=6.44 Hz, 1H), 1.24 (d, J=2.71 Hz, 1H), 1.31 (s, 1H),1.68 (m, 4H), 1.86 (m, 2H), 2.56 (m, 1H), 2.88 (s, 3H), 2.95 (m, 2H),3.08 (dd, J=14.07, 6.61 Hz, 1H), 3.29 (m, 2H), 3.69 (s, 3H), 3.90 (s,1H), 4.01 (m, 1H), 4.41 (m, 2H), 4.55 (d, J=15.94 Hz, 1H), 6.13 (d,J=8.82 Hz, 1H), 7.11 (m, 5H), 7.42 (s, 1H), 7.79 (m, 4H), 7.92 (d,J=9.49 Hz, 1H), 8.24 (s, 1H), 8.42 (s, 2H)

Example 473

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J=6.78 Hz, 3H), 0.74 (t, J=7.29Hz, 3H), 0.95 (d, J=6.78 Hz, 1H), 1.07 (s, 2H), 1.19 (m, 2H), 1.43 (dd,J=10.51, 6.10 Hz, 2H), 1.53 (m, 6H), 2.20 (s, 1H), 2.56 (m, 1H), 2.88(s, 3H), 2.99 (m, 2H), 3.14 (m, 1H), 3.34 (m, 1H), 3.63 (s, 1H), 4.01(m, 2H), 4.37 (m, 2H), 4.55 (d, J=15.94 Hz, 1H), 6.13 (d, J=8.48 Hz,1H), 7.09 (m, 5H), 7.42 (s, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.81 (d,J=8.82 Hz, 2H), 7.94 (d, J=9.16 Hz, 1H), 8.24 (s, 1H), 8.42 (s, 2H)

Example 474

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J=6.78 Hz, 3H), 0.74 (t, J=7.46Hz, 3H), 0.85 (m, 1H), 0.98 (dd, J=16.62, 6.44 Hz, 1H), 1.18 (t, J=7.29Hz, 4H), 1.49 (d, J=6.78 Hz, 3H), 1.48 (m, J=35.26 Hz, 6H), 2.18 (d,J=7.12 Hz, 1H), 2.58 (m, 1H), 2.89 (s, 3H), 2.97 (s, 2H), 3.10 (m, 2H),3.32 (d, J=3.05 Hz, 1H), 3.63 (s, 1H), 3.94 (s, 1H), 4.02 (t, J=8.31 Hz,1H), 4.25 (s, 1H), 4.41 (d, J=15.94 Hz, 1H), 4.56 (d, J=16.28 Hz, 1H),4.82 (s, 1H), 6.17 (d, J=8.48 Hz, 1H), 7.12 (m, 5H), 7.43 (s, 1H), 7.76(d, J=8.82 Hz, 2H), 7.79 (d, J=8.82 Hz, 2H), 7.97 (d, J=9.49 Hz, 1H),8.24 (s, 1H), 8.52 (s, 2H)

Example 475

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J=6.44 Hz, 3H), 0.74 (t, J=7.29Hz, 3H), 0.95 (d, J=6.44 Hz, 2H), 1.17 (s, 1H), 1.34 (s, 2H), 1.47 (m,8H), 1.57 (d, J=6.78 Hz, 3H), 2.18 (d, J=6.78 Hz, 1H), 2.55 (m, 1H),2.88 (s, 3H), 2.98 (m, 2H), 3.14 (m, 1H), 3.34 (dd, J=14.24, 3.39 Hz,1H), 3.64 (s, 1H), 4.02 (m, 1H), 4.40 (d, J=16.28 Hz, 1H), 4.55 (d,J=16.28 Hz, 1H), 4.71 (s, 1H), 6.17 (d, J=8.14 Hz, 1H), 7.09 (m, 5H),7.45 (s, 1H), 7.76 (d, J=8.82 Hz, 2H), 7.81 (d, J=8.82 Hz, 2H), 7.98 (d,J=9.16 Hz, 1H), 8.24 (s, 1H), 8.49 (d, J=4.41 Hz, 2H)

Example 476

¹H NMR (300 MHz, CD₃OD) δ ppm 0.66 (d, J=6.78 Hz, 3H), 0.74 (t, J=7.29Hz, 3H), 0.90 (m, 1H), 1.15 (d, J=6.10 Hz, 1H), 1.25 (m, 2H), 1.59 (m,8H), 2.22 (m, 1H), 2.26 (s, 3H), 2.63 (dd, J=13.73, 10.68 Hz, 1H), 3.00(s, 3H), 3.11 (m, 5H), 3.45 (dd, J=14.92, 3.73 Hz, 1H), 3.81 (m, 1H),3.97 (m, 1H), 4.10 (m, 1H), 4.48 (d, J=16.62 Hz, 1H), 4.61 (d, J=16.62Hz, 1H), 7.16 (m, 7H), 7.70 (t, J=7.63 Hz, 1H), 7.76 (d, J=8.82 Hz, 2H),7.82 (d, J=8.48 Hz, 2 H), 8.13 (s, 1H)

Example 477

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.61 (d, J=6.99 Hz, 2H), 0.70 (t, J=7.35Hz, 3H), 0.85 (m, 1H), 0.94 (m, 1H), 1.08 (s, 1H), 1.21 (m, 3H), 1.44(d, J=6.99 Hz, 3H), 1.47 (d, J=32.72 Hz, 8H), 1.87 (s, 3H), 2.19 (m,1H), 2.57 (m, 1H), 2.84 (s, 3H), 2.97 (m, 2H), 3.13 (m, 1H), 3.33 (m,1H), 3.60 (s, 2H), 4.42 (s, 2H), 5.10 (dd, J=14.89, 7.17 Hz, 1H), 6.04(d, J=8.46 Hz, 1H), 7.15 (s, 1H), 7.14 (m, 5H), 7.75 (m, 3H), 7.80 (d,J=8.82 Hz, 2H), 8.23 (s, 1H), 8.58 (d, J=8.09 Hz, 1H)

Example 480

¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44Hz, 3H), 1.26 (s, 1H), 1.85 (d, J=7.46 Hz, 2H), 2.09 (s, 1H), 2.87 (d,J=6.78 Hz, 1H), 2.99 (m, 3H), 3.16 (m, 1H), 3.63 (d, J=10.51 Hz, 1H),3.68 (s, 1H), 3.78 (dd, J=10.68, 4.58 Hz, 1H), 3.84 (s, 3H), 4.84 (d,J=8.14 Hz, 1H), 5.12 (s, 1H), 7.26 (m, 5H), 7.71 (d, J=8.48 Hz, 2H),7.78 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 481

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 1.99 (s, 1H), 2.27 (m, 2H), 2.60 (dd, J=13.90, 10.17 Hz, 1H),2.83 (m, 1H), 2.97 (m, 4H), 3.63 (s, 1H), 3.80 (s, 1H), 4.25 (dd,J=8.48, 5.43 Hz, 1H), 5.00 (m, 3H), 6.83 (s, 1H), 7.12 (dd, J=8.65, 4.24Hz, 1H), 7.21 (m, 5H), 7.35 (s, 4H), 7.78 (m, 6H), 8.23 (s, 1H)

Example 482

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (m, 15H), 1.86 (m, 1H), 2.83 (dd,J=13.56, 6.78 Hz, 1H), 2.91 (dd, J=13.73, 4.58 Hz, 1H), 3.01 (m, 2H),3.11 (s, 1H), 3.65 (s, 3H), 3.74 (m, 1H), 3.86 (m, 1H), 4.21 (s, 1H),5.07 (s, 1H), 5.99 (d, J=8.48 Hz, 1H), 7.23 (m, 5H), 7.56 (s, 1H), 7.71(d, J=8.48 Hz, 2H), 7.77 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 483

¹H NMR (300 MHz, CD₃OD) δ ppm 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44Hz, 3H), 1.80 (s, 3H), 2.01 (m, 1H), 2.60 (m, 1H), 2.90 (m, 1H), 2.97(m, 1H), 3.12 (m, 2H), 3.41 (dd, J=14.92, 3.05 Hz, 1H), 3.78 (m, 1H),4.01 (m, 1H), 4.80 (s, 1H), 7.19 (m, 5H), 7.79 (m, 4H), 8.14 (s, 1H)

Example 484

¹H NMR (300 MHz, CDCl₃) δ ppm 0.54 (d, J=6.44 Hz, 3H), 0.75 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.96 (d, J=6.44 Hz, 3H), 1.70 (s, 1H),1.92 (s, 1H), 2.79 (s, 1H), 2.81 (m, 1H), 2.97 (m, 2H), 3.26 (dd,J=14.92, 3.05 Hz, 1H), 3.95 (d, J=4.41 Hz, 2H), 4.19 (s, 1H), 5.30 (m,2H), 5.40 (m, 2H), 5.82 (d, J=8.48 Hz, 1H), 7.23 (m, 5H), 7.40 (d,J=7.46 Hz, 1H), 7.74 (m, 6H), 8.15 (s, 1H), 8.57 (d, J=4.75 Hz, 1H)

Example 485

¹H NMR (300 MHz, CDCl₃) δ ppm 0.60 (d, J=6.78 Hz, 3H), 0.83 (s, 1H),0.85 (m, 9H), 1.26 (s, 1H), 1.86 (s, 1H), 2.12 (m, 1H), 2.92 (d, J=8.14Hz, 2H), 3.05 (d, J=4.75 Hz, 1H), 3.12 (d, J=8.14 Hz, 1H), 3.19 (m, 1H),3.80 (s, 1H), 3.91 (s, 1H), 4.12 (s, 1H), 5.09 (s, 1H), 5.23 (s, 2H),6.28 (s, 1H), 7.21 (dd, J=13.39, 6.61 Hz, 7H), 7.30 (m, 1H), 7.71 (d,J=8.14 Hz, 2H), 7.78 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 486

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44Hz, 2H), 1.90 (m, 1H), 2.10 (s, 6H), 3.02 (m, 1H), 3.17 (m, 3H), 3.97(m, 1H), 4.09 (d, J=14.92 Hz, 1H), 4.19 (m, 1H), 4.28 (m, 1H), 6.96 (m,5H), 7.05 (d, J=8.48 Hz, 1H), 7.23 (m, 6H), 7.30 (s, 1H), 7.71 (d,J=8.48 Hz, 2H), 7.80 (d, J=8.48 Hz, 2H), 8.02 (s, 1H), 8.15 (s, 1H)

Example 487

¹H NMR (300 MHz, CDCl₃) δ ppm 0.61 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 6H), 1.86 (m, 1H), 2.10 (d, J=5.76 Hz, 1H),2.90 (m, 2H), 3.04 (m, 1H), 3.10 (d, J=7.80 Hz, 2H), 3.15 (d, J=4.07 Hz,1H), 3.83 (dd, J=8.31, 3.90 Hz, 1H), 3.89 (dd, J=8.14, 5.43 Hz, 1H),4.19 (m, 1H), 4.89 (d, J=1.36 Hz, 1H), 5.07 (s, 2H), 6.23 (d, J=8.14 Hz,1H), 7.20 (m, 5H), 7.33 (m, 5H), 7.60 (s, 1H), 7.71 (d, J=8.48 Hz, 2H),7.80 (d, J=8.48 Hz, 2H), 8.15 (s, 1H)

Example 488

¹H NMR (300 MHz, CDCl₃) δ ppm 0.89 (t, J=6.44 Hz, 6H), 1.08 (d, J=6.44Hz, 3H), 1.84 (dd, J=14.24, 7.12 Hz, 1H), 2.80 (dd, J=14.24, 10.17 Hz,2H), 2.97 (m, 2H), 3.11 (m, 5H), 3.86 (m, 1H), 3.96 (dd, J=7.80, 1.70Hz, 1H), 4.20 (m, J=4.75 Hz, 2H), 5.10 (s, 2H), 5.40 (d, J=6.78 Hz, 1H),6.60 (d, J=7.80 Hz, 1H), 7.21 (m, 4H), 7.34 (m, 5H), 7.72 (d, J=8.48 Hz,2H), 7.80 (d, J=8.48 Hz, 2H), 8.16 (s, 1H)

Example 489

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (dd, J=6.78, 5.09 Hz, 3H), 0.92 (m,3H), 1.65 (s, 2H), 1.85 (d, J=2.71 Hz, 4H), 2.11 (m, 3H), 2.11 (m, 2H),3.46 (m, 1H), 3.85 (m, 6H), 4.13 (dd, J=10.17, 6.10 Hz, 1H), 5.04 (m,1H), 5.22 (s, 1H), 7.26 (m, 5H), 7.74 (m, 4H), 8.16 (s, 1H)

Example 490

¹H NMR (300 MHz, CDCl₃) δ ppm 0.84 (d, J=6.44 Hz, 3H), 0.89 (d, J=6.78Hz, 3H), 1.81 (s, 1H), 2.82 (m, 1H), 2.98 (m, 2H), 3.15 (m, 1H), 3.83(s, 2H), 4.88 (m, 3H), 6.32 (s, 1H), 6.90 (m, 1H), 7.26 (m, 6H), 7.37(m, J=5.43, 5.43 Hz, 1H), 7.70 (d, J=8.48 Hz, 2H), 7.76 (d, J=8.82 Hz,2H), 8.17 (m, 2H)

Example 491

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (dd, J=10.34, 6.61 Hz, 6H), 1.88 (m,1H), 2.95 (m, 6H), 3.19 (m, 1H), 3.75 (m, 1H), 3.88 (s, 1H), 4.13 (s,1H), 5.29 (m, 2H), 5.71 (s, 1H), 6.44 (m, 1H), 7.20 (t, J=7.46 Hz, 4H),7.42 (m, 3H), 7.72 (q, J=8.48 Hz, 4H), 7.85 (m, 1H), 8.15 (s, 1H), 8.61(d, J=4.75 Hz, 1H)

Example 492

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (dd, J=6.10, 3.39 Hz, 6H), 0.88 (dd,J=6.44, 3.05 Hz, 6H), 1.42 (s, 9H), 1.89 (m, 1H), 2.89 (m, 4H), 3.09 (m,5H), 3.84 (s, 2H), 4.15 (s, 1H), 4.61 (s, 1H), 6.25 (d, J=7.46 Hz, 1H),7.26 (m, 5H), 7.75 (m, 4H), 8.15 (s, 1H)

Example 493

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (t, J=6.95 Hz, 6H), 0.88 (d, J=6.44Hz, 6H), 1.01 (s, 1H), 1.84 (s, 2H), 2.90 (s, 4H), 3.06 (s, 4H), 3.84(s, 1H), 3.93 (s, 1H), 4.15 (m, 1H), 4.87 (s, 1H), 5.07 (s, 2H), 6.24(s, 1H), 7.21 (m, 5H), 7.36 (m, 5H), 7.71 (d, J=7.80 Hz, 2H), 7.80 (m,2H), 8.15 (s, 1H)

Example 494

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44Hz, 3H), 1.85 (m, 1H), 2.79 (s, 3H), 2.87 (m, 2H), 2.98 (dd, J=12.55,4.41 Hz, 1H), 3.07 (m, 1H), 3.16 (m, 3H), 3.89 (d, J=7.80 Hz, 2H), 4.41(t, J=5.43 Hz, 2H), 4.95 (s, 1H), 7.27 (m, 5H), 7.59 (m, 1 H), 7.72 (d,J=8.48 Hz, 2H), 7.79 (m, 2H), 8.17 (s, 1H)

Example 495

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (dd, J=6.61, 4.24 Hz, 6H), 0.92 (d,J=6.78 Hz, 1H), 1.43 (s, 9H), 1.86 (m, 1H), 2.89 (s, 3H), 2.93 (m, 3H),2.99 (m, 1H), 3.06 (m, 1H), 3.14 (m, 2H), 3.88 (m, 1H), 4.20 (m, 2H),5.11 (d, J=8.14 Hz, 1H), 6.58 (d, J=8.14 Hz, 1H), 7.25 (m, 5H), 7.49 (m,1H), 7.72 (d, J=8.82 Hz, 2H), 7.81 (m, 3H), 8.16 (s, 1H)

Example 496

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44Hz, 3H), 1.43 (s, 1H), 1.66 (m, 2H), 1.86 (d, J=7.12 Hz, 1H), 2.10 (m,1H), 2.85 (m, 2H), 3.02 (m, 3H), 3.18 (m, 1H), 3.42 (m, 1H), 3.56 (d,J=7.46 Hz, 1H), 3.86 (m, 3H), 4.15 (m, 1H), 4.93 (d, J=8.82 Hz, 1H),5.02 (d, J=4.07 Hz, 1H), 5.21 (dd, J=6.27, 3.22 Hz, 1H), 7.25 (m, 5H),7.67 (s, 1H), 7.75 (m, 4H), 8.16 (s, 1H)

Example 497

¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44Hz, 3H), 1.34 (m, 1H), 1.84 (s, 2H), 2.17 (s, 1H), 2.85 (m, 2H), 2.94(d, J=5.76 Hz, 2H), 3.02 (m, 4H), 3.11 (s, 1H), 3.46 (m, 1H), 3.88 (m,3H), 4.13 (dd, P10.17, 6.44 Hz, 1H), 5.05 (d, J=3.73 Hz, 1H), 5.21 (s,1H), 7.27 (m, 5H), 7.60 (s, 1H), 7.74 (m, 4H), 8.16 (s, 1H)

Example 498

¹H NMR (300 MHz, CD₃OD) δ ppm 0.83 (d, J=6.78 Hz, 3H), 0.89 (m, 3H),1.99 (d, J=7.12 Hz, 1H), 2.67 (dd, J=13.90, 10.51 Hz, 1H), 2.92 (m, 1H),2.99 (d, J=9.16 Hz, 1H), 3.04 (dd, J=8.48, 4.75 Hz, 1H), 3.12 (dd,J=14.41, 8.31 Hz, 3H), 3.36 (d, J=5.09 Hz, 1H), 3.49 (d, J=11.87 Hz,1H), 3.83 (m, 1H), 4.05 (s, 1H), 4.52 (dd, J=8.31, 4.92 Hz, 1H), 4.80(s, 4H), 5.09 (s, 2H), 7.14 (dd, J=8.14, 4.07 Hz, 1H), 7.20 (d, J=4.41Hz, 4H), 7.30 (d, J=8.82 Hz, 1H), 7.34 (m, 3H), 7.76 (d, J=8.48 Hz, 2H),7.83 (m, 2H), 8.13 (s, 1H)

Example 499

¹H NMR (300 MHz, CD₃OD) δ ppm 0.83 (d, J=6.78 Hz, 3H), 0.89 (d, J=6.44Hz, 3H), 1.63 (m, 1H), 1.75 (m, 1H), 1.99 (s, 3H), 2.01 (m, 1H), 2.31(m, 2H), 2.66 (dd, J=13.73, 10.68 Hz, 1H), 2.93 (dd, J=14.24, 7.46 Hz,2H), 3.02 (m, 2H), 3.09 (m, 1H), 3.16 (dd, J=14.07, 3.90 Hz, 1H), 3.45(d, J=16.95 Hz, 1H), 3.80 (m, 1H), 4.02 (s, 1H), 4.10 (m, 1H), 5.06 (d,J=6.10 Hz, 2H), 7.14 (m, 1H), 7.20 (d, J=4.41 Hz, 5H), 7.31 (m, 4H),7.77 (d, J=8.48 Hz, 2H), 7.84 (d, J=8.48 Hz, 2H), 8.13 (s, 1H)

Example 500

¹H NMR (300 MHz, CD₃OD) δ ppm 0.83 (m, 9H), 0.89 (m, 3H), 1.25 (m, 2H),1.49 (m, 1H), 2.01 (s, 1H), 2.66 (dd, J=13.90, 10.51 Hz, 1H), 2.93 (dd,J=13.56, 7.12 Hz, 2H), 2.99 (d, J=9.16 Hz, 1H), 3.07 (m, 2H), 3.17 (dd,J=13.73, 3.90 Hz, 1H), 3.45 (dd, J=15.26, 2.71 Hz, 1H), 3.79 (m, 1H),4.01 (dd, J=9.32, 5.93 Hz, 1H), 5.05 (m, 2H), 7.13 (m, 1H), 7.19 (d,J=4.41 Hz, 5H), 7.29 (dd, J=8.31, 5.26 Hz, 5H), 7.76 (d, J=8.14 Hz, 2H),7.83 (m, 2H), 8.13 (s, 1H)

Example 501

¹H NMR (300 MHz, CD₃OD) δ ppm 0.82 (s, 9H), 0.84 (d, J=6.78 Hz, 3H),0.88 (d, J=6.78 Hz, 3H), 1.98 (m, 1H), 2.62 (dd, J=13.90, 10.85 Hz, 1H),2.95 (dd, J=13.90, 7.12 Hz, 2H), 3.05 (m, 2H), 3.13 (m, 1H), 3.44 (dd,J=14.58, 3.39 Hz, 1H), 3.78 (m, 1H), 3.86 (s, 1H), 4.10 (m, 1H), 5.07(s, 2H), 7.06 (d, J=7.12 Hz, 1H), 7.13 (t, J=7.29 Hz, 2H), 7.20 (m, 3H),7.32 (m, 5H), 7.76 (d, J=8.82 Hz, 2H), 7.82 (d, J=8.48 Hz, 2H), 8.13 (s,1H)

Example 502

¹H NMR (300 MHz, CD₃OD) δ ppm 0.83 (d, J=6.44 Hz, 3H), 0.89 (m, 3H),1.43 (m, 6H), 1.93 (s, 1H), 2.59 (t, J=6.95 Hz, 2H), 2.66 (dd, J=13.90,10.51 Hz, 1H), 2.94 (m, 2H), 3.05 (m, 2H), 3.15 (m, 1H), 3.48 (d,J=15.60 Hz, 1H), 3.79 (m, 1H), 3.96 (m, 1H), 4.05 (d, J=7.12 Hz, 1H),5.07 (m, 2H), 7.12 (m, 1H), 7.19 (m, 5H), 7.30 (dd, J=8.48, 5.43 Hz,5H), 7.76 (d, J=8.48 Hz, 2H), 7.84 (d, J=8.48 Hz, 2H), 8.13 (s, 1H)

Example 503

¹H NMR (300 MHz, CD₃OD) δ ppm 0.83 (d, J=6.78 Hz, 3H), 0.88 (d, J=6.78Hz, 3H), 1.97 (m, 1H), 2.64 (dd, J=15.09, 9.32 Hz, 1H), 2.71 (d, J=10.17Hz, 1H), 2.84 (m, 2H), 2.94 (m, 1H), 3.02 (dd, J=8.65, 6.61 Hz, 2H),3.11 (m, 1H), 3.38 (dd, J=15.09, 2.88 Hz, 1H), 3.79 (m, 1H), 4.04 (m,1H), 4.25 (dd, J=9.16, 5.09 Hz, 1H), 5.02 (m, 2H), 6.74 (s, 1H), 7.12(m, 1H), 7.19 (m, 7H), 7.29 (m, 6H), 7.55 (s, 1H), 7.74 (d, J=8.14 Hz,2H), 7.82 (m, 2H), 8.11 (s, 1H)

Example 504

¹H NMR (300 MHz, CD₃OD) δ ppm 0.82 (d, J=6.44 Hz, 3H), 0.85 (d, J=6.44Hz, 3H), 1.92 (m, 1H), 2.01 (s, 1H), 2.65 (dd, J=13.90, 9.83 Hz, 1H),2.80 (d, J=14.58 Hz, 1H), 2.85 (m, 1H), 2.91 (m, 2H), 2.98 (m, 2H), 3.08(m, 2H), 3.71 (d, J=9.83 Hz, 1H), 3.99 (s, 1H), 4.32 (m, 1H), 4.97 (d,J=7.12 Hz, 2H), 6.95 (s, 1H), 6.98 (d, J=7.12 Hz, 1H), 7.07 (m, 2H),7.16 (m, 6H), 7.26 (m, 6H), 7.54 (d, J=7.80 Hz, 1H), 7.73 (d, J=8.48 Hz,2H), 7.80 (m, 2H), 8.09 (s, 1H)

Example 505

¹H NMR (300 MHz, CD₃OD) δ ppm 0.82 (d, J=6.78 Hz, 3H), 0.88 (d, J=6.78Hz, 3H), 1.05 (d, J=6.10 Hz, 3H), 1.97 (d, J=14.24 Hz, 1H), 2.70 (dd,J=13.90, 10.17 Hz, 1H), 2.91 (dd, J=13.73, 6.95 Hz, 2H), 2.99 (d, J=9.16Hz, 1H), 3.04 (m, 2H), 3.12 (m, 2H), 3.44 (dd, J=14.92, 3.05 Hz, 1H),3.68 (d, J=15.60 Hz, 1H), 3.79 (m, 2H), 3.89 (d, J=15.60 Hz, 1H), 4.10(m, 2H), 5.11 (m, 2H), 7.12 (m, 1H), 7.19 (m, 5H), 7.31 (m, 5H), 7.79(m, 4H), 8.13 (s, 1H)

Example 506

¹H NMR (300 MHz, CD₃OD) δ ppm 0.84 (d, J=6.44 Hz, 3H), 0.89 (d, J=6.44Hz, 3H), 2.01 (s, 2H), 2.44 (dd, J=16.78, 7.97 Hz, 1H), 2.93 (dd,J=14.41, 7.29 Hz, 2H), 3.04 (m, 3H), 3.14 (m, 1H), 3.40 (d, J=2.71 Hz,1H), 3.57 (s, 3H), 3.79 (m, 1H), 3.98 (s, 1H), 4.40 (t, J=6.95 Hz, 1H),5.09 (m, 2H), 7.13 (m, 1H), 7.19 (m, 5H), 7.32 (m, 5H), 7.80 (m, 4H),8.13 (s, 1H)

Example 507

¹H NMR (300 MHz, CD₃OD) δ ppm 0.70 (d, J=6.78 Hz, 3H), 0.77 (t, J=7.46Hz, 3H), 1.03 (m, 2H), 1.24 (m, 2H), 1.57 (m, 8H), 2.22 (dd, J=14.92,7.46 Hz, 1H), 2.66 (dd, J=13.90, 10.85 Hz, 1H), 3.02 (d, J=7.12 Hz, 1H),3.08 (m, 1H), 3.18 (m, 3H), 3.45 (dd, J=14.92, 3.73 Hz, 1H), 3.80 (dd,J=6.44, 3.39 Hz, 1H), 3.85 (m, 1H), 4.12 (m, 1H), 5.16 (s, 2H), 7.09 (m,1H), 7.20 (m, 5H), 7.33 (dd, J=6.95, 5.59 Hz, 1H), 7.45 (d, J=7.80 Hz,1H), 7.79 (m, 4H), 8.13 (s, 1H), 8.50 (d, J=4.07 Hz, 1H)

Example 508

¹H NMR (300 MHz, CD₃OD) δ ppm 0.70 (d, J=6.78 Hz, 3H), 0.77 (t, J=7.46Hz, 3H), 0.98 (m, 1H), 1.12 (m, 1H), 1.24 (m, 2H), 1.58 (m, 8H), 2.23(m, 1H), 2.66 (dd, J=13.90, 10.85 Hz, 1H), 3.05 (m, 2H), 3.19 (m, 2H),3.44 (s, 3H), 3.45 (m, 1H), 3.81 (m, 1H), 3.85 (d, J=7.12 Hz, 1H), 4.11(m, 1H), 4.52 (s, 2H), 5.14 (s, 2H), 7.09 (m, 1H), 7.20 (m, 5H), 7.36(dd, J=15.60, 7.80 Hz, 2H), 7.79 (m, 5H), 8.12 (s, 1H)

Example 509

¹H NMR (300 MHz, CD₃OD) δ ppm 0.84 (s, 9H), 1.15 (s, 1H), 1.23 (s, 1H),1.56 (d, J=3.68 Hz, 8H), 2.22 (dd, J=14.71, 6.99 Hz, 1H), 2.65 (dd,J=13.79, 10.48 Hz, 1H), 3.06 (m, 1H), 3.15 (m, 1H), 3.44 (s, 3H), 3.46(m, 3H), 3.82 (m, 1H), 3.87 (s, 1H), 4.14 (m, 1H), 4.53 (s, 2H), 5.15(s, 2H), 7.07 (d, J=6.62 Hz, 1H), 7.18 (m, 5H), 7.37 (dd, J=16.73, 7.91Hz, 2H), 7.79 (m, 5H), 8.13 (s, 1H)

Example 510

¹H NMR (300 MHz, CDCl₃) δ ppm 0.85 (d, J=6.62 Hz, 3H), 0.89 (d, J=6.62Hz, 3H), 1.80 (m, 1H), 2.84 (dd, J=13.24, 6.99 Hz, 1H), 2.96 (m, 2H),3.05 (d, J=5.15 Hz, 2H), 3.14 (m, 1H), 3.85 (s, 2H), 4.93 (d, J=7.35 Hz,1H), 5.02 (s, 2H), 7.20 (d, J=8.09 Hz, 4H), 7.27 (m, 3H), 7.55 (s, 1H),7.73 (q, J=8.58 Hz, 4H), 8.17 (s, 1H), 8.56 (dd, J=4.96, 1.65 Hz, 1H)

Example 511

¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (d, J=6.62 Hz, 3H), 0.90 (d, J=6.62Hz, 3H), 1.82 (d, J=7.72 Hz, 1H), 2.84 (dd, J=13.60, 6.99 Hz, 1H), 2.97(m, 1H), 3.06 (m, 2H), 3.17 (m, 1H), 3.64 (s, 1H), 3.89 (s, 2H), 5.02(d, J=3.31 Hz, 2H), 7.07 (d, J=4.41 Hz, 2H), 7.28 (m, 5H), 7.70 (d,J=8.46 Hz, 2H), 7.77 (m, 2H), 8.13 (s, 1H), 8.16 (s, 1H), 8.54 (d,J=5.88 Hz, 2H)

Example 512

¹H NMR (300 MHz, CDCl₃) δ ppm 0.85 (m, 3H), 0.90 (m, 3H), 1.86 (m, 1H),2.82 (m, 1H), 2.98 (m, 2H), 3.15 (m, 1H), 3.62 (s, 1H), 3.85 (s, 2H),4.88 (s, 1H), 5.20 (m, 2H), 6.90 (m, 1H), 7.24 (m, 6H), 7.76 (m, 5H),8.17 (m, 2H), 8.78 (m, 1H)

Example 513

¹H NMR (300 MHz, CD₃OD) δ ppm 0.85 (d, J=7.46 Hz, 12H), 0.89 (d, J=6.78Hz, 3H), 1.98 (m, 1H), 2.59 (m, 1H), 2.97 (m, 1H), 3.04 (m, 2H), 3.12(m, 2H), 3.20 (m, 3H), 3.45 (dd, J=14.92, 3.39 Hz, 1H), 3.63 (s, 3H),3.78 (m, 1H), 4.09 (m, 1H), 4.14 (s, 1H), 7.03 (m, 2H), 7.18 (m, 6H),7.31 (m, 1H), 7.76 (m, 2H), 7.82 (d, J=8.82 Hz, 2H), 8.14 (s, 1H)

Example 514

¹H NMR (300 MHz, CD₃OD) δ ppm 0.63 (s, 9H), 0.81 (d, J=6.78 Hz, 3H),0.86 (d, J=6.78 Hz, 3H), 1.97 (m, 1H), 2.59 (dd, J=14.58, 11.53 Hz, 1H),2.89 (m, 1H), 3.06 (m, 2H), 3.21 (d, J=4.07 Hz, 4H), 3.26 (d, J=4.07 Hz,1H), 3.43 (m, 1H), 3.63 (s, 2H), 3.72 (m, 1H), 4.08 (s, 1H), 4.17 (m,1H), 6.95 (m, 1H), 7.12 (m, 2H), 7.23 (m, 6H), 7.31 (m, 1H), 7.74 (m,2H), 7.79 (m, 2H), 8.12 (s, 1H)

Example 515

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.80 (m, 3H),0.83 (m, 3H), 0.90 (t, J=5.93 Hz, 3H), 1.00 (m, 1H), 1.69 (m, 1H), 1.97(m, J=6.78 Hz, 1H), 2.64 (m, 1H), 2.94 (m, 2H), 3.02 (d, J=5.76 Hz, 1H),3.07 (m, 2H), 3.17 (m, 2H), 3.45 (m, 1H), 3.76 (m, 1H), 3.92 (m, 1H),4.09 (m, 4H), 7.15 (m, 1H), 7.22 (m, 5H), 7.80 (m, 4H), 8.14 (s, 1H)

Example 516

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.78 (m, 3H),0.83 (m, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.97 (m, 1H), 1.26 (m, 1H), 1.64(d, J=6.78 Hz, 1H), 2.00 (m, 1H), 2.62 (m, 1H), 2.94 (m, 1H), 3.03 (m,1H), 3.08 (m, 1H), 3.13 (d, J=4.41 Hz, 1H), 3.20 (m, 4H), 3.45 (m, 1H),3.66 (m, 2H), 3.78 (m, 1H), 4.09 (m, 1H), 4.13 (m, 1H), 6.98 (m, 1H),7.09 (m, 3H), 7.12 (m, 1H), 7.18 (d, J=6.78 Hz, 3H), 7.23 (t, J=3.90 Hz,1H), 7.31 (m, 1H), 7.76 (m, 2H), 7.83 (m, 2H), 8.13 (s, 1H)

Example 517

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.77 (d, J=7.12Hz, 3H), 0.84 (m, 3H), 0.89 (d, J=6.44 Hz, 3H), 1.28 (s, 1H), 1.67 (d,J=9.83 Hz, 1H), 2.02 (d, J=5.76 Hz, 1H), 2.62 (dd, J=13.90, 10.85 Hz,1H), 2.97 (m, 2H), 3.07 (m, 1H), 3.14 (m, 1H), 3.21 (d, J=2.71 Hz, 2H),3.25 (s, 2H), 3.47 (m, 1H), 3.64 (m, 2H), 3.79 (d, J=3.39 Hz, 1H), 4.08(m, 1H), 4.13 (d, J=7.12 Hz, 1H), 7.10 (m, 1H), 7.20 (m, 5H), 7.60 (d,J=1.70 Hz, 1H), 7.72 (d, J=8.48 Hz, 1H), 7.80 (m, 4H), 7.96 (d, J=2.03Hz, 1H), 8.13 (s, 1H)

Example 518

¹H NMR (300 MHz, CD₃OD) δ ppm 0.82 (d, J=6.44 Hz, 3H), 0.89 (d, J=6.78Hz, 3H), 1.36 (m, 2H), 1.47 (m, 2H), 1.95 (s, 1H), 2.64 (dd, J=13.90,10.51 Hz, 1H), 2.94 (m, 2H), 3.05 (m, 5H), 3.16 (m, 2H), 3.49 (s, 1H),3.78 (m, 1H), 3.98 (t, J=7.12 Hz, 1H), 4.08 (s, 1H), 5.08 (m, 2H), 7.14(m, 1H), 7.19 (m, 5H), 7.30 (dd, J=7.97, 4.92 Hz, 5H), 7.81 (m, 4H),8.14 (s, 1H)

Example 519

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.62 Hz, 3H), 0.86 (s, 3H),0.95 (s, 9H), 1.81 (dd, J=14.89, 8.27 Hz, 4H), 2.80 (dd, J=13.05, 6.43Hz, 1H), 2.95 (d, J=5.15 Hz, 2H), 3.04 (d, J=12.87 Hz, 1H), 3.25 (s,1H), 3.74 (s, 1H), 4.00 (s, 1H), 4.36 (s, 1H), 7.22 (m, 5H), 7.40 (s,1H), 7.66 (d, J=8.46 Hz, 2H), 7.74 (d, J=8.82 Hz, 2H), 8.16 (s, 1H)

Example 520

¹H NMR (300 MHz, CD₃OD) δ ppm 0.80 (d, J=6.62 Hz, 3H), 0.89 (d, J=6.62Hz, 3H), 1.95 (m, 1H), 2.53 (dd, J=13.97, 9.93 Hz, 1H), 2.90 (m, 3H),2.98 (dd, J=9.93, 4.04 Hz, 1H), 3.07 (m, 1H), 3.56 (m, 2H), 3.88 (m,1H), 7.01 (s, 5H), 7.4 g (m, 4H), 7.78 (m, 4H), 8.08 (s, 1H), 8.15 (s,1H)

Example 525

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (d, J=6.44 Hz, 3H), 0.70 (d, J=6.78Hz, 3H), 0.81 (dd, J=6.61, 3.22 Hz, 6H), 1.94 (m, 2H), 2.42 (dd,J=13.39, 11.02 Hz, 1H), 2.59 (m, 1H), 2.63 (s, 3H), 2.80 (dd, J=13.73,6.61 Hz, 1H), 2.90 (m, 1H), 3.00 (m, 2H), 3.19 (m, 2H), 3.59 (s, 1H),3.75 (d, J=10.85 Hz, 1H), 3.83 (s, 3H), 3.89 (d, J=10.17 Hz, 1H), 4.33(s, 2H), 4.93 (d, J=6.44 Hz, 1H), 7.07 (m, 7H), 7.22 (s, 1H), 7.72 (d,J=8.82 Hz, 2H), 7.87 (d, J=9.49 Hz, 1H)

Example 526

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.51 (s, 1H),2.13 (m, 1H), 2.68 (t, J=4.41 Hz, 1H), 2.78 (m, 1H), 2.83 (s, 1H), 2.98(m, 2H), 3.06 (m, 2H), 3.16 (m, 2H), 3.33 (dd, J=3.90, 2.20 Hz, 1H),3.66 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 3.86 (m, 1H), 3.87 (s, 2H), 4.17(m, 1H), 4.25 (d, J=14.92 Hz, 1H), 4.42 (m, 2H), 6.40 (d, J=8.82 Hz,1H), 6.99 (m, 3H), 7.16 (m, 5H), 7.29 (m, 1H), 7.73 (d, J=8.82 Hz, 2H)

Example 527

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.37 (t,J=7.63 Hz, 3H), 1.54 (s, 1H), 1.85 (m, 1H), 2.13 (m, 1H), 2.28 (t,J=5.76 Hz, 1H), 2.68 (m, 1H), 2.80 (m, 1H), 3.01 (m, 2H), 3.12 (m, 2H),3.20 (m, 2H), 3.30 (m, 1H), 3.65 (m, 2H), 3.75 (m, 1H), 3.87 (d, J=6.44Hz, 1H), 3.87 (s, 3H), 4.17 (m, 1H), 4.39 (d, J=14.92 Hz, 1H), 4.46 (d,J=16.28 Hz, 1H), 6.42 (d, J=8.82 Hz, 1H), 6.97 (m, 4H), 7.16 (m, 3H),7.73 (d, J=8.82 Hz, 2H)

Example 528

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.83 (s, 1H),2.04 (s, 3H), 2.70 (m, 1H), 2.80 (m, 1H), 2.99 (m, 2H), 3.11 (m, 2H),3.19 (m, 3H), 3.48 (s, 2H), 3.65 (d, J=10.85 Hz, 1H), 3.76 (s, 1H), 3.87(s, 3H), 4.17 (m, 1H), 4.39 (d, J=15.60 Hz, 1H), 4.49 (d, J=15.60 Hz,1H), 4.70 (s, 2H), 6.44 (d, J=9.16 Hz, 1H), 6.99 (d, J=8.82 Hz, 2H),7.10 (s, 1H), 7.16 (m, 5H), 7.72 (d, J=8.82 Hz, 2H)

Example 529

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.15 (m, 1H), 2.73 (m, 1H), 2.80 (m, 1H), 2.99 (m, 2H), 3.13 (m, 3H),3.22 (m, 1H), 3.67 (d, J=10.85 Hz, 1H), 3.77 (m, 1H), 3.87 (s, 3H), 4.20(m, 1H), 4.58 (d, J=15.94 Hz, 1H), 4.73 (d, J=15.94 Hz, 1H), 6.38 (d,J=9.16 Hz, 1H), 6.96 (s, 1H), 6.99 (s, 1H), 7.17 (d, J=3.39 Hz, 1H),7.21 (m, 5H), 7.31 (d, J=3.39 Hz, 1H), 7.71 (m, 2H), 7.74 (d, J=1.70 Hz,2H)

Example 530

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (m, 6H), 0.87 (d, J=6.78 Hz, 3H),0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.12 (s, 1H), 2.28 (s, 3H), 2.29(s, 3H), 2.71 (m, 1H), 2.78 (m, 1H), 2.97 (m, 2H), 3.03 (d, J=2.71 Hz,2H), 3.07 (d, J=5.43 Hz, 3H), 3.12 (d, J=3.05 Hz, 2H), 3.16 (m, 1H),3.67 (d, J=10.85 Hz, 1H), 3.77 (s, 1H), 3.87 (s, 3H), 4.12 (d, J=14.92Hz, 1H), 4.19 (m, 1H), 4.33 (d, J=15.26 Hz, 1H), 6.46 (d, J=8.82 Hz,1H), 6.97 (d, J=8.82 Hz, 1H), 7.19 (m, 5H), 7.40 (m, 4H), 7.71 (s, 1H),7.74 (s, 1H)

Example 531

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (t, J=6.95 Hz, 6H), 0.86 (d, J=6.44Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.31 (t, J=7.46 Hz, 3H), 1.83 (m, 1H),2.10 (m, 1H), 2.65 (m, 1H), 2.78 (m, 1H), 2.93 (m, 4H), 3.03 (m, 1H),3.16 (m, 1H), 3.27 (m, 1H), 3.65 (m, 1H), 3.74 (m, 1H), 3.87 (s, 3H),4.17 (m, 1H), 4.44 (q, J=14.69 Hz, 2H), 6.36 (d, J=8.82 Hz, 1H), 6.98(m, 2H), 7.10 (m, 2H), 7.18 (m, 5H), 7.40 (m, 4H), 7.72 (m, 2H), 7.87(m, 2H)

Example 532

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (t, J=6.61 Hz, 6H), 0.86 (d, J=6.44Hz, 3H), 0.92 (m, 3H), 1.23 (t, J=7.63 Hz, 3H), 1.83 (m, 1H), 2.11 (m,1H), 2.62 (s, 3H), 2.68 (m, 1H), 2.78 (dd, J=12.55, 5.76 Hz, 1H), 2.85(m, 2H), 2.96 (m, 2H), 3.04 (m, 1H), 3.16 (m, 5H), 3.64 (d, J=11.19 Hz,1H), 3.74 (m, 1H), 3.87 (s, 3H), 4.14 (m, 1H), 4.35 (m, 2H), 6.37 (d,J=9.16 Hz, 1H), 6.98 (m, 2H), 7.16 (m, 5H), 7.72 (m, 2H)

Example 533

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.79 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.83 (m, 1H),2.10 (m, 1H), 2.41 (s, 3H), 2.60 (s, 3H), 2.67 (m, 1H), 2.78 (m, 1H),2.96 (dd, J=13.39, 8.65 Hz, 1H), 3.06 (m, 1H), 3.16 (m, 6H), 3.63 (d,J=10.85 Hz, 1H), 3.73 (m, 1H), 3.87 (s, 3H), 4.15 (m, 1H), 4.34 (d,J=3.39 Hz, 2H), 6.38 (d, J=9.16 Hz, 1H), 6.97 (m, 2H), 7.14 (m, 5H),7.72 (m, 2H)

Example 534

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 6H), 0.87 (d, J=6.78 Hz, 3H),0.92 (d, J=6.78 Hz, 3H), 1.84 (m, 1H), 2.16 (dd, J=17.63, 6.78 Hz, 1H),2.78 (m, 3H), 2.94 (d, J=8.48 Hz, 1H), 3.01 (m, 2H), 3.12 (m, 4H), 3.67(d, J=10.85 Hz, 1H), 3.79 (s, 1H), 3.87 (s, 3H), 4.15 (d, J=15.60 Hz,1H), 4.20 (s, 1H), 4.41 (d, J=15.94 Hz, 1H), 6.40 (d, J=8.82 Hz, 1H),6.98 (d, J=9.16 Hz, 2H), 7.19 (m, 5H), 7.33 (d, J=1.70 Hz, 1H), 7.73 (d,J=8.82 Hz, 2H), 7.80 (d, J=1.70 Hz, 1H)

Example 535

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.55 (m, 1H), 1.84 (m, 1H), 2.12 (m,1H), 2.67 (m, 1H), 2.79 (m, 1H), 2.99 (m, 2H), 3.12 (m, 1H), 3.72 (d,J=10.85 Hz, 1H), 3.78 (m, 1H), 3.85 (d, J=3.05 Hz, 1H), 3.87 (s, 3H),4.18 (m, 1H), 4.53 (d, J=14.92 Hz, 2H), 4.64 (d, J=14.58 Hz, 2H), 6.39(d, J=9.16 Hz, 2H), 6.98 (d, J=8.82 Hz, 2H), 7.11 (m, 5H), 7.30 (s, 1H),7.37 (m, 2H), 7.74 (d, J=8.82 Hz, 2H), 7.86 (m, 1H), 7.92 (m, 1H)

Example 536

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=3.73 Hz, 3H), 0.81 (d, J=3.39Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.15 (m, 1H), 2.73 (m, 1H), 2.79 (m, 1H), 2.97 (m, 1H), 3.06 (m, 3H),3.17 (m, 4H), 3.67 (d, J=10.85 Hz, 1H), 3.80 (s, 3H), 3.87 (s, 3H), 3.90(m, J=2.71 Hz, 1H), 4.20 (m, 1H), 4.51 (d, J=15.26 Hz, 1H), 4.76 (d,J=15.26 Hz, 1H), 6.36 (d, J=8.82 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.16(m, 5H), 7.32 (m, 4H), 7.72 (d, J=9.16 Hz, 2H)

Example 537

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.78 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.83 (m, 1H), 2.15 (m, 1H), 2.77 (m,4H), 2.97 (m, 3H), 3.04 (m, 3H), 3.12 (m, 2H), 3.70 (s, 3H), 3.78 (m,1H), 3.87 (s, 3H), 419 (m, 1H), 4.36 (d, J=15.26 Hz, 1H), 4.65 (d,J=15.26 Hz, 1H), 6.41 (d, J=7.12 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.15(m, 9H), 7.57 (d, J=7.80 Hz, 1H), 7.72 (d, J=9.16 Hz, 1H)

Example 538

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.44 Hz, 3H), 0.87 (d, J=6.44Hz, 6H), 0.92 (d, J=6.78 Hz, 3H), 1.83 (dd, J=14.58, 6.78 Hz, 1H), 2.17(m, 1H), 2.77 (m, 3H), 3.00 (m, 2H), 3.16 (m, 5H), 3.71 (d, J=10.85 Hz,1H), 3.78 (m, 1H), 3.87 (s, 3H), 3.89 (d, J=3.05 Hz, 1H), 4.20 (m, 1H),4.53 (d, J=15.26 Hz, 1H), 4.77 (d, J=15.26 Hz, 1H), 6.45 (d, J=8.82 Hz,1H), 6.98 (d, J=9.16 Hz, 2H), 7.18 (m, 5H), 7.38 (d, J=8.48 Hz, 1H),7.53 (m, 1H), 7.73 (d, J=8.82 Hz, 2H), 7.80 (d, J=8.14 Hz, 1H), 8.05 (d,J=8.82 Hz, 1H), 8.14 (d, J=8.48 Hz, 1H)

Example 539

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.70 (m, 2H),1.83 (m, 1H), 1.94 (m, 3H), 2.13 (m, 1H), 2.29 (m, 1H), 2.69 (m, 2H),2.80 (m, 2H), 3.00 (m, 2H), 3.11 (m, 2H), 3.19 (m, 1H), 3.49 (m, 1H),3.64 (d, J=10.85 Hz, 1H), 3.73 (d, J=11.87 Hz, 1H), 3.87 (s, 3H), 4.17(m, 1H), 4.38 (t, J=15.26 Hz, 2H), 6.41 (d, J=9.16 Hz, 1H), 6.83 (s,1H), 6.98 (d, J=8.82 Hz, 2H), 7.16 (m, 5H), 7.72 (d, J=8.82 Hz, 1H)

Example 540

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (t, J=6.95 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.17 (m, 1H), 2.75 (m,2H), 2.86 (m, 2H), 2.96 (m, 1H), 3.13 (m, 7H), 3.25 (m, 1H), 3.29 (m,2H), 3.64 (d, J=10.85 Hz, 1H), 3.79 (m, 1H), 3.87 (s, 3H), 4.20 (m, 1H),4.39 (d, J=15.94 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.20 (m, 5H), 7.50(s, 1H), 7.72 (d, J=9.16 Hz, 2H)

Example 541

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.78 Hz, 6H), 0.87 (m, 3H),0.92 (d, J=6.78 Hz, 3H), 1.25 (dd, J=6.95, 1.87 Hz, 6H), 1.84 (m, 1H),2.12 (m, 1H), 2.76 (m, 2H), 2.98 (m, 2H), 3.19 (m, 6H), 3.67 (d, J=10.85Hz, 1H), 3.78 (m, 2H), 3.87 (s, 3H), 4.19 (m, 1H), 4.42 (d, J=15.60 Hz,1H), 4.61 (d, J=15.60 Hz, 1H), 6.43 (d, J=9.16 Hz, 1H), 6.98 (d, J=8.82Hz, 2H), 7.16 (m, 5H), 7.43 (s, 1H), 7.73 (d, J=8.82 Hz, 2H)

Example 542

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd, J=9.32, 6.61 Hz, 6H), 0.86 (d,J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.00 (m, 3H), 1.80 (m, 3H),2.13 (m, 2H), 2.76 (m, 4H), 2.98 (m, 2H), 3.19 (m, 5H), 3.67 (d, J=11.19Hz, 1H), 3.78 (m, 1H), 3.87 (s, 3H), 4.18 (m, 1H), 4.42 (d, J=15.60 Hz,1H), 4.60 (m, 1H), 6.49 (d, J=8.82 Hz, 1H), 6.98 (d, J=8.82 Hz, 2H),7.16 (m, 5H), 7.43 (s, 1H), 7.73 (d, J=9.16 Hz, 2H)

Example 543

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=4.78 Hz, 3H), 0.82 (d, J=4.78Hz, 3H), 0.87 (d, J=6.62 Hz, 3H), 0.92 (d, J=6.62 Hz, 3H), 1.84 (m, 1H),2.16 (s, 1H), 2.75 (m, 1H), 2.82 (d, J=9.19 Hz, 2H), 2.94 (d, J=8.09 Hz,1H), 3.04 (d, J=3.31 Hz, 2H), 3.16 (m, 4H), 3.68 (d, J=10.66 Hz, 1H),3.81 (s, 1H), 3.87 (s, 3H), 4.23 (s, 1H), 4.33 (d, J=15.81 Hz, 1H), 4.61(d, J=15.81 Hz, 1H), 6.42 (s, 1H), 6.90 (m, 1H), 6.98 (m, 2H), 7.19 (m,5H), 7.48 (m, 1H), 7.72 (m, 2H), 7.79 (d, J=4.04 Hz, 1H)

Example 544

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (t, J=6.95 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.17 (m, 1H), 2.75 (m,1H), 2.93 (m, 3H), 3.13 (m, 5H), 3.30 (m, 1H), 3.64 (d, J=10.85 Hz, 1H),3.79 (m, 1H), 3.87 (s, 3H), 4.20 (m, 1H), 4.39 (d, J=15.94 Hz, 1H), 4.57(d, J=16.28 Hz, 1H), 6.44 (d, J=8.82 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H),7.19 (m, 5H), 7.50 (s, 1H), 7.72 (d, J=9.16 Hz, 2H)

Example 545

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.13 (m, 1H), 2.75 (m, 2H), 2.97 (m, 2H), 3.12 (m, 4H), 3.21 (m, 3H),3.65 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 4.18 (m, 1H), 4.38(d, J=15.60 Hz, 1H), 4.51 (d, J=16.28 Hz, 1H), 4.62 (s, 2H), 6.45 (d,J=9.16 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.14 (s, 1H), 7.19 (m, 5H),7.72 (d, J=8.82 Hz, 2H)

Example 546

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.86 (d, J=6.44 Hz, 3H),0.92 (d, J=6.44 Hz, 3H), 1.22 (t, J=7.29 Hz, 3H), 1.83 (m, 1H), 2.14 (m,1H), 2.72 (m, 2H), 2.80 (m, 2H), 2.98 (m, 2H), 3.17 (m, 6H), 3.67 (d,J=10.85 Hz, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 4.18 (m, 1H), 4.42 (d,J=15.60 Hz, 1H), 4.59 (d, J=15.60 Hz, 1H), 6.39 (d, J=9.16 Hz, 1H), 6.98(d, J=8.82 Hz, 2H), 7.16 (m, 5H), 7.42 (s, 1H), 7.72 (d, J=8.82 Hz, 2H)

Example 547

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44Hz, 3H), 0.95 (s, 9H), 1.11 (m, 1H), 1.83 (dd, J=14.75, 6.61 Hz, 1H),2.51 (q, J=8.82 Hz, 1H), 2.70 (s, 3H), 2.80 (m, 1H), 3.01 (m, 2H), 3.11(m, 4H), 3.29 (m, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 3.98 (s, 1H), 4.18(m, 1H), 4.44 (d, J=7.46 Hz, 2H), 6.11 (d, J=9.49 Hz, 1H), 6.94 (s, 1H),6.98 (d, J=9.16 Hz, 2H), 7.14 (m, 5H), 7.73 (d, J=9.16 Hz, 2H)

Example 548

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.84 (dd,J=13.73, 6.95 Hz, 6H), 0.92 (d, J=6.78 Hz, 3H), 0.99 (m, 1H), 1.36 (m,1H), 1.84 (m, 1H), 1.94 (m, 1H), 2.69 (s, 3H), 2.76 (m, 3H), 2.97 (m,1H), 3.13 (m, 6H), 3.76 (m, 2H), 3.87 (s, 3H), 4.18 (m, 1H), 4.36 (d,J=15.26 Hz, 1H), 4.46 (d, J=15.26 Hz, 1H), 6.40 (d, J=8.82 Hz, 1H), 6.93(s, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.16 (m, 5H), 7.73 (d, J=8.82 Hz, 2H)

Example 549

¹H NMR (300 MHz, CDCl₃) δ ppm 0.90 (d, J=3.39 Hz, 3H), 0.92 (d, J=3.39Hz, 3H), 1.89 (m, 1H), 2.43 (m, 2H), 2.69 (s, 3H), 2.77 (m, 1H), 2.91(m, 2H), 3.14 (m, 9H), 3.87 (s, 3H), 4.26 (m, 1H), 4.41 (d, J=12.55 Hz,1H), 4.71 (m, 1H), 5.23 (s, 1H), 5.85 (s, 1H), 6.79 (d, J=9.16 Hz, 1H),6.98 (s, 1H), 6.99 (d, J=7.80 Hz, 2H), 7.15 (m, 5H), 7.75 (d, J=8.82 Hz,2H)

Example 550

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.11 (m, 1H), 2.71 (m, 2H), 2.79 (m, 2H), 2.96 (m, 1H), 3.02 (m, 1H),3.16 (m, 7H), 3.65 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 4.17(m, 1H), 4.40 (d, J=15.26 Hz, 1H), 4.50 (d, J=15.94 Hz, 1H), 5.33 (s,2H), 6.41 (d, J=8.82 Hz, 1H), 6.98 (d, J=8.82 Hz, 2H), 7.14 (s, 1H),7.18 (m, 5H), 7.72 (d, J=9.16 Hz, 2H)

Example 551

¹H NMR (300 MHz, CDCl₃) δ ppm 0.90 (d, J=6.44 Hz, 6H), 1.67 (s, 2H),1.89 (m, 2H), 2.09 (m, 2H), 2.40 (m, 1H), 2.70 (s, 3H), 2.81 (dd,J=14.41, 11.02 Hz, 1H), 2.90 (d, J=7.46 Hz, 2H), 3.09 (m, 4H), 3.15 (m,3H), 3.87 (s, 3H), 4.30 (m, 2H), 4.54 (d, J=15.26 Hz, 1H), 5.52 (s, 1H),6.10 (s, 1H), 6.74 (d, J=8.82 Hz, 1H), 6.97 (m, 1H), 7.00 (d, J=8.82 Hz,2H), 7.16 (m, 5H), 7.74 (d, J=9.16 Hz, 2H)

Example 552

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.13 (m, 1H), 2.70 (m, 1H), 2.78 (m, 1H), 2.99 (m, 2H), 3.14 (m, 5H),3.68 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 4.20 (m, 1H), 4.47(d, J=4.07 Hz, 2H), 6.36 (d, J=9.16 Hz, 1H), 6.61 (s, 1H), 6.98 (d,J=8.82 Hz, 2H), 7.11 (m, 2H), 7.21 (m, 6H), 7.43 (d, J=8.14 Hz, 1H),7.53 (m, 1H), 7.73 (d, J=9.16 Hz, 2H)

Example 553

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (dd, J=9.83, 6.78 Hz, 6H), 0.87 (d,J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.14 (m, 1H),2.78 (m, 5H), 3.06 (m, 7H), 3.70 (d, J=11.19 Hz, 1H), 3.82 (d, J=3.39Hz, 1H), 3.87 (s, 3H), 4.21 (m, 1H), 4.38 (d, J=15.26 Hz, 1H), 4.67 (d,J=15.26 Hz, 1H), 6.43 (d, J=8.82 Hz, 1H), 6.98 (d, J=8.82 Hz, 2H), 7.16(m, 6H), 7.56 (m, 1H), 7.80 (d, J=8.14 Hz, 1H), 8.03 (s, 1H), 8.12 (d,J=8.48 Hz, 1H), 8.83 (d, J=2.03 Hz, 1H)

Example 554

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd, J=6.61, 3.56 Hz, 3H), 0.88 (m,6H), 0.92 (m, 3H), 1.67 (s, 1H), 1.85 (d, J=6.78 Hz, 1H), 2.03 (m, 2H),2.16 (m, 1H), 2.59 (m, 1H), 2.79 (m, 2H), 2.90 (m, 1H), 3.10 (m, 4H),3.66 (m, 1H), 3.80 (d, J=5.76 Hz, 1H), 3.87 (s, 2H), 4.07 (s, 1H), 4.10(m, 2H), 4.20 (m, 1H), 4.32 (m, 1H), 4.94 (m, 1H), 5.02 (m, 1H), 5.37(d, J=11.19 Hz, 1H), 6.43 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.19 (m,5H), 7.73 (m, 2H)

Example 555

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.14 (s, 3H), 2.70 (m, 2H), 2.79 (m, 2H), 2.99 (m, 2H), 3.17 (m, 5H),3.66 (d, J=10.85 Hz, 1H), 3.77 (m, 1H), 3.87 (s, 3H), 3.95 (s, 2H), 4.18(m, 1H), 4.42 (m, 2H), 6.49 (d, J=9.16 Hz, 1H), 6.97 (m, 2H), 7.08 (m,1H), 7.14 (m, 5H), 7.72 (d, J=9.16 Hz, 2H)

Example 556

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.14 (m, 1H), 2.72 (m, 1H), 2.80 (m, 2H), 2.95 (m, 1H), 3.07 (m, 2H),3.16 (m, 2H), 3.24 (m, 2H), 3.66 (d, J=10.85 Hz, 1H), 3.79 (m, 1H), 3.87(s, 3H), 4.08 (s, 2H), 4.18 (m, 1H), 4.44 (m, 2H), 6.51 (d, J=9.16 Hz,1H), 6.98 (d, J=9.16 Hz, 2H), 7.14 (s, 1H), 7.18 (m, 5H), 7.72 (d,J=8.82 Hz, 2H)

Example 557

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.85 (m, 9H),1.88 (m, 1H), 2.23 (s, 3H), 2.88 (m, 5H), 3.12 (m, 7H), 3.60 (d, J=10.51Hz, 1H), 3.87 (s, 3H), 3.95 (m, 1H), 4.17 (m, 1H), 4.35 (m, 2H), 6.71(s, 1H), 6.97 (m, 2H), 7.18 (m, 5H), 7.73 (m, 2H)

Example 558

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.44 Hz, 3H), 0.87 (d, J=6.78Hz, 6H), 0.92 (d, J=6.44 Hz, 3H), 1.85 (m, 1H), 2.18 (m, 1H), 2.78 (m,3H), 3.00 (m, 2H), 3.18 (m, 4H), 3.71 (d, J=10.85 Hz, 1H), 3.78 (s, 1H),3.87 (d, J=3.05 Hz, 3H), 4.21 (m, 1H), 4.51 (d, J=15.94 Hz, 1H), 4.80(d, J=15.60 Hz, 1H), 6.43 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.18 (m,7H), 7.33 (d, J=7.46 Hz, 1H), 7.44 (m, 2H), 7.73 (m, 2H), 8.17 (d,J=8.48 Hz, 1H)

Example 559

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.84 (t, J=6.95Hz, 6H), 0.91 (d, J=6.44 Hz, 3H), 0.97 (m, 1H), 1.29 (m, 1H), 1.82 (dd,J=14.75, 6.95 Hz, 1H), 1.97 (m, 1H), 2.79 (m, 2H), 2.99 (m, 3H), 3.10(m, 2H), 3.24 (t, J=7.80 Hz, 2H), 3.76 (d, J=10.85 Hz, 2H), 3.85 (s,3H), 3.87 (s, 3H), 4.22 (m, 1H), 4.61 (d, J=15.26 Hz, 1H), 4.81 (m, 1H),6.35 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.15 (m, 6H), 7.35 (m, 3H), 7.71(m, 2H), 7.79 (m, 1H)

Example 560

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.44 Hz, 3H), 0.86 (t, J=6.78Hz, 6H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.16 (m, 1H), 2.75 (m,3H), 3.01 (m, 3H), 3.14 (m, 3H), 3.72 (d, J=11.19 Hz, 1H), 3.79 (m, 1H),3.87 (m, 3H), 398 (s, 3H), 4.19 (m, 1H), 4.45 (s, 1H), 4.79 (d, J=15.26Hz, 1H), 6.41 (d, J=9.16 Hz, 1H), 6.76 (s, 1H), 6.98 (d, J=9.16 Hz, 2H),7.18 (m, 6H), 7.50 (t, J=7.46 Hz, 1H), 7.68 (s, 1H), 7.72 (m, 2H), 8.00(s, 1H), 8.16 (d, J=8.14 Hz, 1H)

Example 561

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (t, J=6.10 Hz, 3H), 0.86 (m, 6H),0.92 (d, J=6.78 Hz, 3H), 1.85 (m, 3H), 2.16 (m, 1H), 2.78 (m, 2H), 3.00(m, 2H), 3.21 (m, 4H), 3.70 (d, J=10.85 Hz, 1H), 3.78 (m, 1H), 3.87 (s,3H), 4.22 (d, J=9.49 Hz, 1H), 4.54 (d, J=15.94 Hz, 1H), 4.84 (d, J=15.94Hz, 1H), 6.40 (d, J=8.82 Hz, 1H), 6.98 (d, J=8.82 Hz, 2H), 7.17 (m, 6H),7.72 (m, 2H), 7.78 (m, 2H), 8.05 (m, 1H), 8.12 (m, 1H)

Example 562

¹H NMR (300 MHz, CDCl₃) δ ppm 0.91 (d, J=3.73 Hz, 3H), 0.93 (d, J=4.07Hz, 3H), 1.87 (m, 1H), 2.37 (dd, J=14.58, 6.44 Hz, 1H), 2.49 (m, 1H),2.63 (d, J=4.75 Hz, 3H), 2.70 (m, 3H), 2.75 (m, 1H), 2.92 (m, 2H), 3.13(m, 5H), 3.79 (s, 1H), 3.87 (s, 3H), 4.23 (m, 1H), 4.41 (m, 2H), 4.64(dd, J=8.14, 6.44 Hz, 1H), 5.79 (s, 1H), 6.78 (d, J=9.16 Hz, 1H), 6.99(m, 3H), 7.16 (m, 6H), 7.75 (m, 2H)

Example 563

¹H NMR (300 MHz, CDCl₃) δ ppm 0.91 (d, J=5.09 Hz, 3H), 0.93 (d, J=4.75Hz, 3H), 0.99 (t, J=7.29 Hz, 3H), 1.88 (dd, J=13.73, 6.95 Hz, 1H), 2.35(dd, J=14.58, 6.44 Hz, 1H), 2.48 (q, J=8.48 Hz, 1H), 2.69 (s, 3H), 2.76(m, 1H), 2.92 (m, 2H), 3.14 (m, 6H), 3.81 (m, 1H), 3.87 (s, 3H), 3.91(d, J=3.39 Hz, 1H), 4.22 (dd, J=9.66, 5.26 Hz, 1H), 4.41 (m, 2H), 4.64(dd, J=8.31, 6.61 Hz, 1H), 5.76 (s, 1H), 6.75 (d, J=8.82 Hz, 1H), 6.99(m, 3H), 7.16 (m, 6H), 7.75 (m, 2H)

Example 564

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.83 (d, J=7.12Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.01 (m, 1H),1.32 (m, 1H), 1.84 (m, 3H), 1.97 (m, 1H), 2.78 (m, 3H), 3.06 (m, 4H),3.81 (m, 2H), 3.87 (s, 3H), 3.91 (d, J=2.71 Hz, 1H), 4.23 (m, 1H), 4.79(m, 2H), 6.47 (d, J=8.82 Hz, 1H), 6.97 (m, 2H), 7.15 (m, 6H), 7.27 (s,1H), 7.59 (m, 1H), 7.75 (m, 2H), 8.15 (d, J=8.48 Hz, 2H), 8.88 (d,J=4.41 Hz, 1H)

Example 565

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.86 (m, 6H),0.91 (m, 3H), 0.99 (m, 1H), 1.31 (m, 1H), 1.85 (m, 1H), 2.00 (m, 1H),2.48 (m, 2H), 2.90 (m, 1H), 3.05 (m, 4H), 3.18 (m, 1H), 3.41 (m, 1H),3.76 (m, 1H), 3.83 (s, 1H), 3.87 (s, 3H), 4.13 (m, 1H), 4.49 (m, 2H),6.99 (m, 5H), 7.08 (m, 2H), 7.14 (m, 2H), 7.25 (m, 1H), 7.59 (s, 2H),7.78 (m, 2H), 8.16 (s, 1H)

Example 566

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (t, J=6.61 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 1.16 (d, J=6.44 Hz, 1H), 1.29 (d, J=11.19 Hz, 1H), 1.59 (m,8H), 2.13 (m, 2H), 2.71 (m, 1H), 2.90 (m, 1H), 3.11 (m, 4H), 3.48 (d,J=5.76 Hz, 3H), 3.67 (d, J=10.85 Hz, 1H), 3.80 (m, 1H), 3.86 (d, J=3.73Hz, 3H), 3.88 (s, 1H), 4.23 (m, 1H), 4.45 (q, J=15.60 Hz, 2H), 4.70 (d,J=4.07 Hz, 2H), 6.53 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.11 (d, J=2.37Hz, 1H), 7.20 (m, 6H), 7.72 (d, J=9.16 Hz, 2-H)

Example 567

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.88 (m, 6H),0.90 (m, 3H), 1.02 (m, 1H), 1.41 (m, 1H), 1.88 (m, 1H), 1.98 (m, 1H),2.51 (dd, J=13.73, 11.36 Hz, 1H), 2.62 (m, 1H), 2.90 (dd, J=13.73, 6.95Hz, 1H), 3.00 (dd, J=14.41, 8.65 Hz, 2H), 3.13 (m, 3H), 3.24 (m, 2H),3.41 (dd, J=14.58, 3.73 Hz, 1H), 3.77 (m, 1H), 3.87 (d, J=11.19 Hz, 1H),3.87 (s, 3H), 4.16 (m, 1H), 4.52 (d, J=15.94 Hz, 1H), 4.78 (m, 1H), 7.08(m, 4H), 7.16 (m, 3H), 7.46 (d, J=8.48 Hz, 1H), 7.59 (m, 1H), 7.76 (m,3H), 7.92 (d, J=8.14 Hz, 1H), 8.02 (d, J=8.48 Hz, 1H), 8.33 (d, J=8.48Hz, 1H)

Example 568

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.82 (t, J=7.29Hz, 3H), 0.96 (m, 1H), 1.18 (m, 1H), 1.29 (m, 2H), 1.59 (m, 8H), 1.95(m, 1H), 2.10 (dd, J=15.26, 7.80 Hz, 1H), 2.77 (m, 2H), 2.91 (dd,J=13.22, 7.12 Hz, 1H), 3.06 (m, 3H), 3.17 (m, 2H), 3.77 (m, 1H), 3.80(s, 3H), 3.87 (s, 3H), 4.24 (m, 1H), 4.50 (d, J=15.26 Hz, 1H), 4.76 (d,J=15.26 Hz, 1H), 6.38 (d, J=9.16 Hz, 1H), 6.98 (m, 2H), 7.15 (m, 6H),7.31 (m, 3H), 7.72 (m, 2H), 7.75 (m, 1H)

Example 569

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62 (d, J=6.44 Hz, 3H), 0.78 (m, 6H),0.82 (d, J=3.05 Hz, 3H), 0.89 (m, 1H), 1.73 (s, 1H), 1.97 (m, 1H), 2.41(dd, J=13.73, 11.02 Hz, 1H), 2.61 (t, J=7.12 Hz, 1H), 2.80 (dd, J=13.90,6.78 Hz, 1H), 2.97 (m, 3H), 3.10 (m, 1H), 3.21 (dd, J=14.58, 2.37 Hz,1H), 3.38 (s, 3H), 3.44 (m, 1H), 3.51 (s, 1H), 3.60 (m, 1H), 3.83 (s,3H), 3.89 (m, 2H), 4.37 (s, 2H), 4.68 (s, 2H), 4.93 (d, J=6.44 Hz, 1H),7.07 (m, 7H), 7.41 (s, 1H), 7.72 (d, J=8.82 Hz, 2H), 7.87 (d, J=9.16 Hz,1H)

Example 570

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.86 (dd, J=8.82,6.78 Hz, 6H), 0.92 (d, J=6.78 Hz, 3H), 1.02 (m, 1H), 1.35 (m, 1H), 1.84(m, 1H), 1.97 (d, J=10.85 Hz, 1H), 2.79 (m, 1H), 2.88 (s, 3H), 2.96 (s,3H), 3.08 (m, 2H), 3.79 (m, 2H), 3.87 (s, 3H), 4.20 (m, 2H), 4.49 (d,J=15.60 Hz, 1H), 6.41 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.18 (m, 5H),7.47 (m, 3H), 7.58 (m, 1H), 7.73 (m, 2H), 8.02 (s, 1H)

Example 571

¹H NMR (300 MHz, CDCl₃) δ ppm 0.87 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44Hz, 3H), 0.96 (s, 9H), 1.84 (m, 1H), 2.56 (q, J=8.93 Hz, 1H), 2.71 (dd,J=14.41, 10.68 Hz, 1H), 2.82 (m, 1H), 2.97 (m, 2H), 3.10 (m, 4H), 3.29(m, 1H), 3.56 (dd, J=7.80, 5.43 Hz, 1H), 3.82 (m, 3H), 3.87 (d, J=4.07Hz, 3H), 3.97 (d, J=11.53 Hz, 1H), 4.24 (m, 1H), 4.57 (d, J=15.26 Hz,1H), 4.75 (m, 1H), 6.13 (d, J=9.16 Hz, 1H), 6.99 (m, 2H), 7.12 (m, 5H),7.32 (m, 3H), 7.72 (m, 2H), 7.76 (m, 1H)

Example 572

¹H NMR (300 MHz, CDCl₃) δ ppm 0.89 (d, J=6.78 Hz, 3H), 1.90 (d, J=6.44Hz, 1H), 2.31 (s, 1H), 2.68 (m, 3H), 2.79 (s, 2H), 2.89 (t, J=7.80 Hz,2H), 3.08 (m, 4H), 3.25 (m, 1H), 3.49 (s, 1H), 3.75 (s, 1H), 3.87 (s,3H), 3.91 (d, J=7.46 Hz, 1H), 3.97 (t, J=4.75 Hz, 2H), 4.46 (d, J=13.90Hz, 5H), 6.97 (m, 4H), 7.20 (m, 5H), 7.75 (m, 2H), 7.98 (m, 1H)

Example 573

¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (m, 6H), 1.87 (m, 2H), 2.65 (s, 1H),2.69 (s, 3H), 2.88 (m, 2H), 3.05 (m, 1H), 3.27 (m, 2H), 3.57 (dd,J=14.07, 7.63 Hz, 2H), 3.57 (dd, J=14.07, 7.63 Hz, 1H), 3.86 (d, J=3.39Hz, 3H), 3.92 (m, 1H), 4.23 (dd, J=14.41, 4.92 Hz, 1H), 4.33 (m, 2H),4.43 (m, 2H), 4.51 (d, J=2.37 Hz, 1H), 4.73 (d, J=11.19 Hz, 2H), 5.43(s, 1H), 6.98 (m, 5H), 7.16 (m, 3H), 7.22 (d, J=6.10 Hz, 1H), 7.59 (m,1H), 7.73 (m, 2H)

Example 574

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.85 (m, 6H),0.92 (d, J=6.44 Hz, 3H), 0.99 (m, 1H), 1.39 (d, J=25.77 Hz, 1H), 1.86(m, 1H), 1.96 (s, 1H), 2.73 (m, 1H), 2.79 (m, 2H), 2.96 (m, 1H), 3.01(m, 1H), 3.14 (m, 5H), 3.48 (s, 3H), 3.76 (m, 2H), 3.88 (m, 3H), 4.19(d, J=9.49 Hz, 1H), 4.35 (d, J=15.60 Hz, 1H), 4.55 (s, 2H), 4.58 (m,1H), 6.40 (d, J=8.82 Hz, 1H), 6.98 (m, 2H), 7.12 (d, J=8.14 Hz, 1H),7.19 (m, 5H), 7.31 (d, J=7.46 Hz, 1H), 7.67 (t, J=7.63 Hz, 1H), 7.72 (m,2H)

Example 575

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (m, 9H), 0.86 (t, J=7.29 Hz, 3H),1.02 (m, 1H), 1.43 (m, 2H), 1.83 (m, 1H), 2.02 (d, J=13.56 Hz, 1H), 2.34(d, J=5.09 Hz, 3H), 2.85 (m, 3H), 3.08 (m, 5H), 3.78 (d, J=10.85 Hz,1H), 3.87 (s, 3H), 3.95 (m, 1H), 4.20 (m, 2H), 4.51 (d, J=16.28 Hz, 1H),4.64 (d, J=3.39 Hz, 1H), 6.57 (d, J=7.80 Hz, 1H), 6.98 (m, 2H), 7.10(dd, J=5.09, 1.70 Hz, 1H), 7.18 (m, 5H), 7.72 (m, 3H), 8.55 (d, J=5.09Hz, 1H)

Example 576

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J=6.44 Hz, 3H), 0.81 (m, 9H),0.93 (m, 1H), 1.29 (m, 1H), 1.75 (s, 1H), 1.95 (m, 1H), 2.41 (dd,J=13.56, 10.85 Hz, 1H), 2.59 (m, 1H), 2.80 (dd, J=13.56, 6.78 Hz, 1H),2.92 (dd, J=13.90, 8.48 Hz, 2H), 3.07 (m, 1H), 3.21 (m, 1H), 3.59 (m,1H), 3.84 (s, 3H), 3.88 (m, 2H), 4.47 (d, J=3.05 Hz, 2H), 4.93 (d,J=6.44 Hz, 1H), 6.98 (m, 1H), 7.07 (dd, J=14.92, 8.14 Hz, 7H), 7.48 (m,1H), 7.57 (s, 1H), 7.72 (m, 2H), 7.91 (m, 1H), 7.96 (m, 1H), 8.11 (d,J=7.80 Hz, 1H), 8.63 (d, J=4.07 Hz, 1H)

Example 577

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.25 Hz, 3H), 0.86 (m, 6H),0.92 (d, J=6.62 Hz, 3H), 1.00 (m, 1H), 1.37 (m, 1H), 1.84 (m, 1H), 1.96(m, 1H), 2.76 (m, 2H), 2.97 (m, 1H), 3.02 (dd, J=11.95, 3.13 Hz, 1H),3.10 (m, 2H), 3.27 (m, 2H), 3.76 (m, 2H), 3.87 (m, 4H), 4.13 (m, 1H),4.20 (m, 1H), 4.52 (m, 2H), 6.40 (d, J=9.19 Hz, 1H), 6.97 (m, 2H), 7.16(m, 6H), 7.37 (dd, J=8.46, 4.41 Hz, 1H), 7.73 (m, 2H), 8.21 (m, 1H),8.65 (dd, J=4.78, 1.84 Hz, 1H), 9.15 (d, J=2.21 Hz, 1H)

Example 578

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.93 (d, J=6.62Hz, 3H), 0.95 (s, 9H), 1.84 (dd, J=7.91, 6.43 Hz, 1H), 2.52 (q, J=8.82Hz, 1H), 2.69 (dd, J=14.16, 10.48 Hz, 1H), 2.79 (m, 1H), 2.97 (m, 1H),3.06 (m, 1H), 3.17 (m, 2H), 3.18 (m, 1H), 3.30 (m, 1H), 3.49 (s, 3H),3.75 (m, 1H), 3.85 (d, J=2.57 Hz, 1H), 3.87 (s, 3H), 3.98 (s, 1H), 4.20(m, 1H), 4.47 (m, 2H), 4.71 (s, 2H), 6.14 (d, J=8.82 Hz, 1H), 6.98 (m,2H), 7.11 (s, 1H), 7.15 (m, 5H), 7.73 (m, 2H)

Example 579

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.83 (m, 15H), 1.96 (m, 1H), 2.22 (m,1H), 2.36 (dd, J=13.24, 11.40 Hz, 1H), 2.81 (m, 2H), 2.93 (dd, J=15.26,5.70 Hz, 1H), 3.02 (m, 3H), 3.15 (m, 3H), 3.83 (s, 3H), 3.99 (s, 1H),4.49 (m, 2H), 6.94 (m, 1H), 7.07 (m, 7H), 7.56 (dd, J=7.54, 5.33 Hz,1H), 7.61 (s, 1H), 7.72 (m, 2H), 7.98 (d, J=9.56 Hz, 1H), 8.33 (m, 1H),8.67 (dd, J=4.78, 1.47 Hz, 1H), 9.15 (d, J=1.47 Hz, 1H)

Example 580

¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.62 (m, 3H), 0.78 (m, 6H), 0.82 (m,3H), 0.92 (m, 1H), 1.27 (m, 1H), 1.75 (m, 1H), 1.95 (m, 1H), 2.42 (dd,J=13.43, 10.99 Hz, 1H), 2.60 (m, 1H), 2.71 (s, 3H), 2.81 (m, 1H), 2.92(dd, J=14.04, 8.54 Hz, 1H), 2.97 (dd, J=9.46, 5.80 Hz, 1H), 3.02 (m,1H), 3.09 (m, 1H), 320 (m, 1H), 3.35 (d, J=8.54 Hz, 1H), 3.58 (m, 1H),3.84 (s, 3H), 3.86 (m, 1H), 3.92 (m, 1H), 4.43 (m, 2H), 4.92 (d, J=6.71Hz, 1H), 6.99 (t, Hz, 1H), 7.08 (m, 8H), 7.43 (s, 1H), 7.72 (d, J=8.54Hz, 2H), 7.86 (d, J=9.77 Hz, 1H)

Example 581

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62 (t, J=6.62 Hz, 3H), 0.80 (m, 9H),0.91 (m, 1H), 1.24 (t, J=7.54 Hz, 3H), 1.73 (d, J=8.09 Hz, 1H), 1.95 (m,1H), 2.41 (dd, J=13.42, 11.21 Hz, 1H), 2.60 (m, 1H), 2.80 (m, 2H), 2.92(dd, J=13.79, 8.64 Hz, 2H), 3.04 (m, 4H), 3.08 (m, 1H), 3.21 (m, 3H),3.58 (m, 1H), 3.84 (s, 3H), 3.87 (m, 1H), 4.51 (m, 2H), 4.93 (m, 1H),6.97 (m, 1H), 7.07 (m, 5H), 7.66 (s, 1H), 7.70 (m, 2H), 7.73 (m, 2H),7.90 (d, J=9.56 Hz, 1H), 8.59 (d, J=5.15 Hz, 1H)

Example 582

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.62 Hz, 3H), 0.85 (dd,J=16.55, 6.99 Hz, 6H), 0.91 (d, J=6.62 Hz, 3H), 1.00 (m, 1H), 1.33 (m,1H), 1.83 (dd, J=11.40, 3.68 Hz, 1H), 2.00 (m, 1H), 2.51 (m, 1H), 2.58(s, 3H), 2.91 (m, 2H), 3.06 (m, 6H), 3.23 (m, 3H), 3.40 (dd, J=14.71,3.68 Hz, 1H), 3.75 (m, 1H), 3.82 (s, 1H), 3.87 (s, 3H), 4.11 (m, 1H),4.54 (m, 2H), 7.01 (m, 1H), 7.09 (m, 5H), 7.40 (d, J=8.82 Hz, 1H), 7.46(s, 1H), 7.77 (d, J=8.82 Hz, 2H), 8.23 (d, J=2.21 Hz, 1H), 8.26 (d,J=2.57 Hz, 1H), 9.00 (d, J=2.21 Hz, 1H)

Example 583

¹H NMR (300 MHz, CDCl₃) δ ppm 0.88 (d, J=6.62 Hz, 3H), 0.92 (d, J=6.62Hz, 3H), 0.96 (s, 9H), 1.84 (m, 1H), 2.60 (q, J=8.70 Hz, 1H), 2.72 (dd,J=14.16, 10.48 Hz, 2H), 2.80 (m, 2H), 2.97 (m, 2H), 3.04 (d, J=3.68 Hz,1H), 3.13 (m, 6H), 3.32 (m, 1H), 3.80 (m, 1H), 3.85 (t, J=2.94 Hz, 1H),4.00 (s, 1H), 4.26 (m, 1H), 4.67 (dd, J=65.63, 15.26 Hz, 2H), 6.11 (d,J=9.19 Hz, 1H), 6.99 (m, 2H), 7.11 (m, 5H), 7.23 (m, 1H), 7.73 (m, 2H),8.01 (dd, J=8.09, 1.47 Hz, 1H), 8.39 (dd, J=4.78, 1.47 Hz, 1H)

Example 584

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.62 Hz, 3H), 0.84 (m, 6H),0.92 (d, J=6.25 Hz, 3H), 1.33 (m, 2H), 1.83 (m, 2H), 1.97 (m, 2H), 2.78(m, 3H), 3.01 (m, 2H), 3.14 (m, 2H), 3.80 (m, 3H), 3.87 (s, 3H), 4.10(m, 1H), 4.23 (m, 1H), 4.49 (d, J=15.08 Hz, 1H), 4.79 (d, J=15.44 Hz,1H), 6.33 (d, J=8.82 Hz, 2H), 6.98 (m, 2H), 7.16 (m, 7H), 7.73 (m, 2H),8.00 (dd, J=8.09, 1.47 Hz, 1H), 8.39 (dd, J=4.78, 1.47 Hz, 1H)

Example 585

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.62 Hz, 3H), 0.84 (m, 3H),0.97 (m, 1H), 1.19 (m, 2H), 1.34 (m, 2H), 1.55 (m, 5H), 1.69 (m, 3H),1.86 (m, 1H), 2.26 (m, 1H), 2.52 (m, 3H), 3.01 (m, 1H), 3.17 (m, 1H),3.42 (dd, J=14.71, 4.04 Hz, 1H), 3.79 (m, 2H), 3.87 (s, 3H), 4.13 (m,1H), 4.56 (d, J=5.52 Hz, 2H), 7.05 (m, 6H), 7.17 (m, 3H), 7.51 (s, 1H),7.54 (m, 1H), 7.77 (m, 2H), 8.37 (m, 1H), 8.60 (dd, P4.96, 1.65 Hz, 1H),9.14 (d, J=1.47 Hz, 1H)

Example 586

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58 (d, J=6.62 Hz, 3H), 0.77 (m, 3H),0.87 (q, J=7.23 Hz, 2H), 0.95 (m, 9H), 1.23 (m, 2H), 1.76 (m, 1H), 2.43(m, 1H), 2.59 (m, 1H), 2.80 (d, J=14.71 Hz, 1H), 2.97 (m, 3H), 3.09 (m,1H), 3.21 (d, J=9.56 Hz, 1H), 3.31 (m, 1H), 3.74 (s, 2H), 3.83 (d,J=5.88 Hz, 2H), 4.45 (d, J=15.07 Hz, 2H), 6.97 (m, 1H), 7.07 (m, 7H),7.56 (m, 1H), 7.60 (s, 1H), 7.75 (m, 2H), 7.87 (d, J=9.19 Hz, 1H), 8.33(m, 1H), 8.68 (dd, J=4.78, 1.47 Hz, 1H), 9.15 (d, J=1.47 Hz, 1H)

Example 587

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.14 (m, 1H), 2.75 (m, 3H), 2.99 (m, 3H), 3.19 (m, 4H), 3.66 (d, J=10.85Hz, 1H), 3.76 (m, 1H), 3.87 (s, 3H), 4.19 (m, 3H), 4.38 (d, J=15.26 Hz,1H), 4.47 (d, J=15.60 Hz, 1H), 6.48 (d, J=8.82 Hz, 1H), 6.98 (m, 4H),7.16 (m, 6H), 7.72 (d, J=8.82 Hz, 2H)

Example 588

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.84 (m, 2H),2.02 (s, 3H), 2.15 (m, 1H), 2.76 (m, 4H), 2.95 (m, 1H), 3.05 (dd,J=14.92, 3.73 Hz, 1H), 3.18 (m, 3H), 3.65 (d, J=10.85 Hz, 1H), 3.78 (m,1H), 3.87 (s, 3H), 4.15 (m, 1H), 4.38 (d, J=15.60 Hz, 1H), 4.48 (d,J=15.26 Hz, 1H), 4.70 (d, J=5.43 Hz, 2H), 6.32 (s, 1H), 6.56 (d, J=9.16Hz, 1H), 6.98 (d, J=8.82 Hz, 2H), 7.05 (s, 1H), 7.16 (m, 5H), 7.71 (d,J=9.16 Hz, 2H)

Example 589

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (s, 3H), 0.82 (d, J=6.78 Hz, 3H),0.86 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.15 (m,1H), 2.71 (m, 1H), 2.75 (m, 2H), 2.81 (m, 1H), 2.95 (m, 1H), 3.04 (dd,J=14.41, 11.36 Hz, 1H), 3.11 (m, 4H), 3.21 (m, 1H), 3.64 (d, J=10.85 Hz,1H), 3.78 (m, 1H), 3.87 (s, 3H), 4.17 (m, 1H), 4.44 (q, J=15.37 Hz, 2H),4.92 (s, 2H), 6.55 (d, J=9.16 Hz, 1H), 6.98 (d, J=9.16 Hz, 2H), 7.09 (s,1H), 7.17 (m, 5H), 7.72 (d, J=9.16 Hz, 2H)

Example 590

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.61 Hz, 6H), 0.86 (d, J=6.44Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.83 (m, 1H), 2.16 (m, 1H), 2.70 (s,1H), 2.75 (d, J=2.03 Hz, 6H), 2.80 (m, 1H), 2.94 (m, 1H), 3.00 (dd,J=12.04, 3.22 Hz, 1H), 3.10 (dd, J=9.32, 4.92 Hz, 2H), 3.16 (m, 3H),3.24 (m, 1H), 3.65 (d, J=10.85 Hz, 1H), 3.78 (m, 1H), 3.87 (s, 3H), 4.19(m, 1H), 4.28 (s, 2H), 4.49 (m, 2H), 6.45 (d, J=8.82 Hz, 1H), 6.97 (m,2H), 7.17 (m, 5H), 7.25 (s, 1H), 7.72 (m, 2H)

Example 591

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.16 (m, 1H), 2.72 (m, 1H), 2.79 (dd, J=13.73, 6.27 Hz, 2H), 2.92 (m,1H), 2.98 (s, 3H), 3.06 (dd, J=14.24, 3.73 Hz, 2H), 3.18 (m, 4H), 3.64(d, J=10.85 Hz, 1H), 3.79 (m, 1H), 3.87 (s, 3H), 4.18 (m, 1H), 4.41 (m,2H), 4.60 (d, J=6.10 Hz, 2H), 5.51 (t, J=6.27 Hz, 1H), 6.61 (d, J=9.16Hz, 1H), 6.98 (m, 2H), 7.08 (s, 1H), 7.18 (m, 5H), 7.72 (m, 2H)

Example 592

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.79 (d, J=6.44Hz, 3H), 0.84 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.86 (m, 1H),2.14 (m, 1H), 2.71 (m, 2H), 2.81 (m, 2H), 2.99 (m, 2H), 3.19 (m, 4H),3.69 (d, J=10.85 Hz, 1H), 3.82 (s, 1H), 3.87 (s, 3H), 4.22 (s, 1H), 4.54(m, 2H), 6.88 (m, 1H), 6.98 (d, J=8.82 Hz, 2H), 7.13 (d, J=6.10 Hz, 5H),7.45 (s, 1H), 7.72 (d, J=9.16 Hz, 2H), 8.02 (s, 1H)

Example 593

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.15 (m, 1H), 2.69 (m, 1H), 2.78 (m, 2H), 2.94 (d, J=8.14 Hz, 1H), 2.98(dd, J=5.76, 2.71 Hz, 1H), 3.04 (d, J=3.05 Hz, 1H), 3.13 (m, 3H), 3.21(m, 1H), 3.66 (d, J=10.85 Hz, 1H), 3.71 (s, 3H), 3.78 (m, 1H), 3.87 (s,3H), 4.17 (m, 1H), 4.42 (m, 2H), 4.63 (d, J=6.10 Hz, 2H), 5.53 (s, 1H),6.60 (d, J=9.16 Hz, 1H), 6.97 (m, 2H), 7.06 (s, 1H), 7.16 (m, 5H), 7.72(m, 2H)

Example 594

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (dd, J=9.16, 6.44 Hz, 6H), 0.86 (d,J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.83 (dd, J=14.41, 6.61 Hz,1H), 2.14 (m, 1H), 2.72 (m, 1H), 2.80 (m, 2H), 2.97 (s, 3H), 3.16 (m,7H), 3.66 (d, J=10.85 Hz, 1H), 3.79 (m, 1H), 3.87 (s, 3H), 4.20 (m, 1H),4.47 (m, 2H), 4.59 (s, 2H), 6.55 (d, J=9.16 Hz, 1H), 6.98 (d, J=9.16 Hz,2H), 7.18 (m, 6H), 7.71 (m, 2H)

Example 595

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.86 (d, J=6.44 Hz, 3H),0.91 (d, J=6.78 Hz, 3H), 1.39 (t, J=7.29 Hz, 6H), 1.83 (m, 1H), 2.15 (m,1H), 2.73 (m, 2H), 2.82 (m, 2H), 2.95 (m, 1H), 3.05 (dd, J=16.28, 3.73Hz, 2H), 3.17 (m, 7H), 3.66 (d, J=10.85 Hz, 1H), 3.78 (m, 1H), 3.87 (s,3H), 4.18 (m, 1H), 4.37 (d, J=15.94 Hz, 1H), 4.57 (s, 2H), 4.57 (m, 1H),6.52 (d, J=9.16 Hz, 1H), 6.98 (m, 2H), 7.17 (m, 5H), 7.24 (s, 1H), 7.72(m, 2H)

Example 596

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 1.15 (d,J=6.78 Hz, 6H), 1.27 (d, J=8.48 Hz, 1H), 2.02 (m, 2H), 2.51 (dd,J=13.90, 11.19 Hz, 1H), 2.59 (m, 1H), 2.90 (m, 1H), 3.02 (m, 2H), 3.10(m, 2H), 3.19 (m, 2H), 3.37 (m, 1H), 3.66 (d, J=9.16 Hz, 1H), 3.74 (m,2H), 3.87 (s, 3H), 3.98 (m, 1H), 4.10 (m, 1H), 4.14 (m, 1H), 7.08 (m,2H), 7.17 (m, 5H), 7.76 (m, 2H), 7.93 (d, J=9.49 Hz, 1H)

Example 597

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.44 Hz, 6H), 0.86 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 2.02 (m, 2H), 2.53 (dd, J=13.73, 11.36Hz, 1H), 2.67 (m, 1H), 2.81 (s, 3H), 2.88 (dd, J=13.73, 6.95 Hz, 1H),2.97 (dd, J=14.58, 8.14 Hz, 1H), 3.05 (m, 1H), 3.14 (m, 2H), 3.24 (m,2H), 3.27 (s, 2H), 3.43 (dd, J=14.75, 3.90 Hz, 1H), 3.72 (d, J=11.19 Hz,1H), 3.78 (m, 1H), 3.87 (s, 2H), 4.16 (d, J=10.85 Hz, 1H), 4.37 (d,J=15.60 Hz, 1H), 4.55 (s, 1H), 4.64 (m, 1H), 4.80 (s, 2H), 7.07 (m, 2H),7.17 (m, 4H), 7.51 (s, 1H), 7.76 (m, 2H), 7.93 (d, J=10.17 Hz, 1H)

Example 598

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (d, J=6.44 Hz, 3H), 0.71 (d, J=6.78Hz, 3H), 0.80 (d, J=3.05 Hz, 3H), 0.82 (d, J=3.05 Hz, 3H), 0.87 (m, 1H),1.96 (d, J=7.12 Hz, 2H), 2.22 (s, 1H), 2.34 (s, 3H), 2.43 (d, J=12.89Hz, 1H), 2.80 (dd, J=13.73, 6.61 Hz, 1H), 2.95 (m, 3H), 3.59 (s, 1H),3.76 (d, J=10.85 Hz, 1H), 3.83 (s, 3H), 3.90 (d, J=8.14 Hz, 1H), 4.40(d, J=5.09 Hz, 1H), 4.47 (s, 2H), 4.93 (d, J=6.44 Hz, 1H), 7.06 (m, 7H),7.37 (s, 1H), 7.64 (s, 1H), 7.72 (d, J=8.82 Hz, 2H), 7.87 (d, J=9.49 Hz,1H)

Example 599

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 0.98 (d, J=6.44 Hz, 1H), 1.18 (s, 1H), 1.33 (m, 3H), 1.55 (s,4H), 1.71 (s, 2H), 1.85 (s, 1H), 2.25 (m, 1H), 2.54 (dd, J=13.73, 11.36Hz, 1H), 2.71 (m, 1H), 2.99 (m, 1H), 3.05 (m, 1H), 3.12 (d, J=8.82 Hz,2H), 3.17 (d, J=4.75 Hz, 2H), 3.23 (m, 2H), 3.45 (dd, J=14.75, 4.24 Hz,1H), 3.80 (dd, J=6.10, 3.73 Hz, 1H), 3.83 (d, J=10.85 Hz, 1H), 3.87 (s,3H), 4.18 (s, 1H), 4.36 (d, J=15.60 Hz, 1H), 4.47 (s, 2H), 4.63 (m, 1H),7.08 (m, 2H), 7.13 (d, J=6.10 Hz, 3H), 7.20 (m, 2H), 7.48 (s, 1H), 7.77(m, 2H)

Example 600

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.83 (m, 6H),0.87 (d, J=3.73 Hz, 3H), 0.95 (m, 1H), 1.28 (s, 1H), 1.90 (m, 3H), 3.82(d, J=10.85 Hz, 1H), 3.86 (s, 3H), 4.27 (m, J=15.26 Hz, 2H), 4.44 (m,1H), 5.41 (s, 1H), 672 (d, J=8.82 Hz, 1H), 6.96 (d, J=8.82 Hz, 2H), 7.11(m, 3H), 7.18 (m, 2H), 7.32 (d, P7.46 Hz, 1H), 7.40 (t, J=7.46 Hz, 1H),7.58 (m, 2H), 7.72 (m, 2H)

Example 601

¹H NMR (300 MHz, CDCl₃) δ ppm 0.90 (d, J=6.78 Hz, 6H), 1.70 (m, 1H),1.87 (dd, J=13.73, 6.95 Hz, 1H), 2.04 (m, 1H), 2.37 (m, 1H), 2.89 (m,2H), 2.99 (m, 1H), 3.12 (m, 2H), 3.17 (m, 2H), 3.25 (m, 1H), 3.45 (m,1H), 3.62 (m, 1H), 3.79 (s, 3H), 3.87 (s, 3H), 3.91 (m, 1H), 4.31 (m,1H), 4.54 (m, 2H), 4.78 (d, J=15.60 Hz, 1H), 6.75 (d, J=8.82 Hz, 1H),7.00 (m, 2H), 7.12 (m, 1H), 7.19 (m, 6H), 7.32 (m, 2H), 7.74 (m, 3H)

Example 603

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.82 (m, 1H),2.08 (m, 1H), 2.25 (d, J=6.44 Hz, 2H), 2.66 (dd, J=13.90, 10.85 Hz, 1H),2.78 (dd, J=13.39, 6.61 Hz, 1H), 2.95 (dd, J=12.89, 2.03 Hz, 1H), 3.08(m, 1H), 3.22 (m, 1H), 3.45 (s, 3H), 3.58 (d, J=17.97 Hz, 1H), 3.81 (m,1H), 3.88 (s, 3H), 3.88 (m, 1H), 4.23 (m, 1H), 4.69 (m, 2H), 4.76 (d,J=7.12 Hz, 2H), 6.22 (d, J=9.16 Hz, 1H), 6.98 (m, 2H), 7.09 (m, 5H),7.19 (s, 1H), 7.72 (m, 2H)

Example 604

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.94 (m, 3H), 1.81 (m, 1H), 2.04 (d,J=3.39 Hz, 1H), 2.05 (m, 1H), 2.63 (dd, J=14.07, 10.68 Hz, 1H), 2.77(dd, J=13.56, 6.44 Hz, 1H), 2.91 (d, J=2.71 Hz, 1H), 2.99 (m, 2H), 3.06(m, 1H), 3.18 (m, 2H), 3.53 (d, J=17.97 Hz, 1H), 3.80 (m, 2H), 3.88 (s,3H), 4.22 (m, 1H), 4.62 (m, 2H), 6.05 (d, P9.49 Hz, 1H), 6.97 (s, 1H),6.98 (m, 5H), 7.05 (m, 2H), 7.33 (m, 1H), 7.42 (m, 1H), 7.72 (m, 2H)

Example 605

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (d, J=6.44 Hz, 3H), 0.86 (d, J=6.78Hz, 3H), 0.91 (t, J=6.78 Hz, 6H), 1.28 (s, 1H), 1.83 (m, 1H), 2.15 (m,1H), 2.70 (m, 1H), 2.78 (dd, J=13.39, 6.61 Hz, 1H), 2.98 (m, 1H), 3.08(dd, J=14.24, 4.41 Hz, 1H), 3.19 (m, 1H), 3.40 (m, 1H), 3.74 (d, J=17.97Hz, 1H), 3.82 (s, 2H), 3.88 (s, 3H), 3.92 (d, P10.85 Hz, 1H), 4.25 (m,1H), 4.98 (m, 2H), 6.17 (d, J=9.49 Hz, 1H), 6.98 (m, 2H), 7.15 (m, 5H),7.33 (d, J=8.48 Hz, 1H), 7.49 (m, 1H), 7.65 (m, 1H), 7.72 (m, 2H), 7.77(d, J=7.80 Hz, 1H), 7.95 (d, J=8.48 Hz, 1H), 8.13 (d, J=8.48 Hz, 1H)

Example 606

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (m, 3H), 1.83 (m, 1H), 2.08 (m,1H), 2.71 (dd, J=13.90, 10.85 Hz, 1H), 2.81 (m, 1H), 2.97 (m, 2H), 3.06(dd, P8.31, 3.56 Hz, 1H), 3.18 (m, 2H), 3.36 (d, J=17.97 Hz, 1H), 3.66(m, 1H), 3.87 (s, 3H), 3.88 (s, 3H), 3.96 (d, J=10.85 Hz, 1H), 4.28 (m,1H), 4.90 (m, 2H), 6.39 (d, J=9.49 Hz, 1H), 6.97 (m, 2H), 7.06 (s, 3H),7.17 (m, 3H), 7.26 (m, 1H), 7.32 (m, 1H), 7.72 (m, 3H)

Example 607

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (d, J=6.44 Hz, 6H), 0.87 (d, J=6.44Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.27 (m, 3H), 2.02 (m, 1H), 2.47 (dd,J=13.56, 11.53 Hz, 1H), 2.89 (m, 1H), 3.02 (m, 3H), 3.23 (dd, J=13.73,3.56 Hz, 1H), 3.40 (dd, J=14.92, 3.73 Hz, 1H), 3.71 (d, J=17.97 Hz, 2H),3.78 (m, 1H), 3.87 (s, 3H), 4.01 (d, J=11.19 Hz, 1H), 4.16 (m, 3H), 4.32(m, 1H), 7.08 (m, 2H), 7.19 (m, 6H), 7.77 (m, 2H), 8.22 (d, J=9.83 Hz,1H)

Example 608

¹H NMR (300 MHz, CDCl₃) δ ppm 0.84 (m, 9H), 0.92 (m, 3H), 1.81 (s, 1H),2.11 (s, 1H), 2.72 (m, 1H), 2.79 (m, 1H), 2.88 (s, 1H), 3.00 (m, 1H),3.08 (dd, J=14.24, 4.41 Hz, 1H), 3.18 (m, 1H), 3.41 (d, J=17.97 Hz, 1H),3.71 (d, J=17.97 Hz, 1H), 3.81 (s, 1H), 3.88 (s, 3H), 3.92 (s, 1H), 3.96(s, 3H), 4.26 (s, 1H), 4.91 (m, 2H), 6.20 (d, J=9.16 Hz, 1H), 6.98 (m,2H), 7.16 (m, 5H), 7.72 (m, 2H), 7.94 (dd, J=8.14, 1.36 Hz, 1H), 8.02(s, 1H), 8:36 (dd, J=4.75, 1.36 Hz, 1H)

Example 609

¹H NMR (300 MHz, CD₃OD) δ ppm 0.80 (d, J=6.78 Hz, 3H), 0.86 (dd, J=6.44,1.70 Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 2.04 (m, 2H), 2.49 (dd, J=13.73,11.70 Hz, 1H), 2.86 (s, 2H), 3.03 (m, 1H), 3.12 (d, J=17.97 Hz, 1H),3.23 (dd, J=13.73, 3.56 Hz, 1H), 3.41 (dd, J=14.92, 3.73 Hz, 1H), 3.78(m, 2H), 3.87 (s, 3H), 3.92 (s, 3H), 4.03 (d, J=11.19 Hz, 1H), 4.15 (m,1H), 4.95 (m, 2H), 7.04 (m, 5H), 7.17 (m, 2H), 7.25 (d, J=2.71 Hz, 1H),7.35 (dd, J=9.32, 2.88 Hz, 1H), 7.41 (d, J=8.82 Hz, 1H), 7.76 (m, 2H),7.84 (d, J=9.16 Hz, 1H), 7.97 (s, 1H), 8.20 (d, J=8.48 Hz, 1H)

Example 610

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.86 (m, 6H),0.93 (d, J=6.44 Hz, 3H), 1.82 (m, 1H), 2.09 (m, 1H), 2.67 (dd, J=14.24,10.85 Hz, 1H), 2.78 (dd, J=13.56, 6.44 Hz, 1H), 2.95 (s, 2H), 3.04 (m,1H), 3.19 (m, 1H), 3.35 (d, J=17.97 Hz, 1H), 3.64 (m, 1H), 3.75 (m, 1H),3.81 (m, 1H), 3.88 (s, 3H), 4.26 (m, 1H), 5.11 (m, 2H), 6.12 (d, J=9.16Hz, 1H), 6.99 (d, J=8.82 Hz, 2H), 7.06 (m, 5H), 7.37 (d, J=2.71 Hz, 1H),7.68 (m, 1H), 7.72 (d, J=9.16 Hz, 2H), 7.76 (m, 1H), 8.02 (s, 1H), 8.19(d, J=8.14 Hz, 1H), 8.30 (d, J=8.14 Hz, 1H), 8.88 (d, J=4.07 Hz, 1H)

Example 611

¹H NMR (300 MHz, CD₃OD) δ ppm 0.82 (d, J=6.78 Hz, 3H), 0.87 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 6H), 2.07 (m, 2H), 2.51 (dd, J=13.56, 11.53Hz, 1H), 2.91 (m, 2H), 3.03 (m, 1H), 3.18 (d, J=18.31 Hz, 1H), 3.26 (d,J=3.39 Hz, 1H), 3.42 (dd, J=14.75, 3.56 Hz, 1H), 3.79 (m, 2H), 3.87 (d,J=18.31 Hz, 1H), 3.87 (s, 3H), 4.04 (d, J=11.19 Hz, 1H), 4.16 (m, 1H),5.06 (m, 2H), 7.07 (m, 2H), 7.16 (m, 5H), 7.67 (d, J=8.48 Hz, 1H), 7.76(m, 2H), 8.06 (d, J=9.49 Hz, 1H), 8.45 (dd, J=9.32, 2.54 Hz, 1H), 8.54(d, J=8.48 Hz, 1H), 8.91 (d, J=2.71 Hz, 1H)

Example 612

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.44 Hz, 3H), 0.85 (d, J=6.44Hz, 6H), 0.92 (t, J=5.93 Hz, 3H), 0.90 (m, 2H), 1.83 (m, 1H), 2.15 (m,1H), 2.71 (m, 1H), 2.79 (dd, J=13.39, 6.61 Hz, 1H), 2.98 (m, 2H), 3.08(dd, J=13.73, 4.24 Hz, 1H), 3.18 (m, 1H), 3.42 (d, J=17.63 Hz, 1H), 3.71(d, J=17.63 Hz, 1H), 3.87 (s, 3H), 3.95 (d, J=10.85 Hz, 1H), 4.26 (s,1H), 4.96 (m, 2H), 6.33 (s, 1H), 6.88 (m, 1H), 6.97 (m, 2H), 7.15 (s,5H), 7.24 (d, J=3.39 Hz, 1H), 7.71 (m, 2H), 7.90 (d, J=15.26 Hz, 2H)

Example 613

¹H NMR (300 MHz, CDCl₃) δ ppm 0.70 (d, J=6.78 Hz, 3H), 0.75 (d, J=6.78Hz, 3H), 0.87 (d, J=3.39 Hz, 3H), 0.89 (d, J=3.39 Hz, 3H), 1.89 (m, 1H),2.05 (m, 1H), 2.21 (s, 3H), 2.24 (s, 1H), 2.76 (dd, J=13.90, 10.85 Hz,1H), 2.88 (s, 1H), 2.94 (m, 1H), 2.99 (d, J=4.07 Hz, 1H), 3.01 (d,J=9.16 Hz, 1H), 3.07 (m, 2H), 3.62 (q, J=17.97 Hz, 2H), 3.88 (s, 3H),4.10 (m, 2H), 4.23 (d, J=9.16 Hz, 1H), 4.74 (m, 2H), 6.83 (s, 1H), 6.99(m, 2H), 7.11 (m, 5H), 7.74 (m, 2H)

Example 614

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=6.78 Hz, 3H), 0.78 (m, 6H),0.82 (d, J=4.07 Hz, 3H), 1.20 (s, 1H), 1.72 (s, 1H), 1.92 (m, 1H), 2.10(s, 3H), 2.38 (dd, J=13.22, 11.53 Hz, 1H), 2.73 (s, 1H), 2.79 (dd,J=13.39, 6.61 Hz, 1H), 2.89 (s, 1H), 293 (m, 1H), 3.05 (m, 1H), 3.09 (m,1H), 3.20 (m, J=3.05 Hz, 1H), 3.59 (s, 1H), 3.76 (d, J=17.97 Hz, 1H),3.84 (s, 3H), 3.94 (d, J=8.82 Hz, 1H), 4.08 (d, J=10.85 Hz, 1H), 4.55(d, J=15.94 Hz, 2H), 4.97 (d, J=6.44 Hz, 1H), 6.90 (s, 1H), 7.01 (m,5H), 7.10 (m, 2H), 7.72 (d, J=8.82 Hz, 2H), 8.19 (d, J=9.49 Hz, 1H)

Example 615

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.87 (d, J=6.44Hz, 6H), 0.90 (d, J=6.44 Hz, 3H), 1.01 (m, 1H), 1.40 (m, 1H), 1.88 (m,1H), 2.00 (m, 1H), 2.48 (dd, J=13.56, 11.53 Hz, 1H), 2.89 (dd, J=13.73,6.95 Hz, 1H), 3.02 (m, 1H), 3.02 (d, J=7.80 Hz, 2H), 3.15 (d, J=18.31Hz, 1H), 3.22 (dd, J=13.56, 3.39 Hz, 1H), 3.41 (dd, J=14.58, 3.73 Hz,1H), 3.77 (m, 2H), 3.87 (s, 3H), 4.12 (m, 1H), 4.18 (m, 1H), 4.82 (m,1H), 4.95 (m, 1H), 6.93 (d, J=2.71 Hz, 1H), 7.03 (m, 6H), 7.16 (m, 1H),7.21 (dd, J=8.99, 2.54 Hz, 1H), 7.28 (d, J=8.48 Hz, 1H), 7.70 (d, J=9.16Hz, 1H), 7.76 (m, 2H), 7.96 (d, J=8.48 Hz, 1H)

Example 616

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (m, 6H), 0.87 (d, J=6.44 Hz, 3H),0.93 (d, J=6.44 Hz, 3H), 1.22 (m, 1H), 1.82 (m, 2H), 2.67 (dd, J=14.24,10.51 Hz, 1H), 2.78 (dd, J=13.39, 6.27 Hz, 1H), 2.97 (m, 3H), 3.05 (dd,J=9.32, 4.92 Hz, 1H), 3.19 (m, 1H), 3.37 (d, J=17.97 Hz, 1H), 3.61 (m,1H), 3.74 (d, J=2.71 Hz, 1H), 3.83 (m, 1H), 3.88 (s, 3H), 3.98 (d,J=11.19 Hz, 1H), 4.26 (m, 1H), 5.08 (m, 2H), 6.12 (d, J=9.16 Hz, 1H),6.99 (m, 2H), 7.05 (m, 6H), 7.35 (d, J=4.41 Hz, 1H), 7.64 (m, 1H), 7.72(d, J=9.16 Hz, 2H), 7.77 (m, 1H), 8.16 (d, J=8.14 Hz, 1H), 8.29 (d,J=7.80 Hz, 1H)

Example 617

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.83 (t, J=7.29Hz, 3H), 0.96 (m, 1H), 1.18 (m, 1H), 1.55 (m, 6H), 1.70 (m, 3H), 1.82(m, 1H), 2.24 (m, 1H), 2.47 (dd, J=13.56, 11.87 Hz, 1H), 2.95 (m, 2H),3.04 (m, 2H), 3.15 (d, J=8.48 Hz, 1H), 3.22 (m, 2H), 3.41 (d, J=4.07 Hz,1H), 3.43 (s, 3H), 3.45 (m, 1H), 3.66 (m, 1H), 3.80 (m, 1H), 4.11 (m,1H), 4.18 (m, 1H), 4.66 (s, 2H), 4.77 (d, J=6.78 Hz, 2H), 6.99 (m, 3H),7.08 (m, 2H), 7.12 (m, 2H), 7.41 (s, 1H), 7.77 (m, 2H)

Example 618

¹H NMR (300 MHz, CD₃OD) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.83 (m, 3H),0.87 (d, J=6.78 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 0.97 (m, 1H), 1.29 (m,1H), 1.80 (dd, J=11.19, 3.39 Hz, 1H), 2.00 (m, 1H), 2.46 (dd, J=13.73,11.70 Hz, 1H), 2.89 (m, 1H), 2.94 (m, 1H), 3.00 (m, 2H), 3.06 (m, 1H),3.22 (dd, J=13.56, 3.39 Hz, 1H), 3.41 (m, 1H), 3.43 (s, 2H), 3.66 (d,J=17.97 Hz, 1H), 3.77 (m, 1H), 3.87 (s, 3H), 4.10 (m, 1H), 4.66 (s, 2H),4.77 (m, 2H), 4.78 (m, 2H), 6.99 (m, 3H), 7.08 (m, 2H), 7.12 (m, 2H),7.41 (s, 1H), 7.77 (m, 2H), 8.20 (d, J=9.83 Hz, 1H)

Example 619

¹H NMR (300 MHz, CD₃OD) δ ppm 0.70 (d, J=6.78 Hz, 3H), 0.83 (t, J=7.29Hz, 3H), 0.98 (m, 9H), 1.28 (m, 1H), 1.78 (m, 1H), 2.44 (dd, J=13.90,11.53 Hz, 1H), 2.95 (dd, J=17.97, 3.39 Hz, 2H), 3.09 (m, 1H), 3.15 (dd,J=10.17, 5.09 Hz, 2H), 3.36 (m, 1H), 3.43 (s, 2H), 3.65 (m, 1H), 3.85(d, J=8.82 Hz, 1H), 3.88 (m, 3H), 3.94 (m, 1H), 4.07 (m, 2H), 4.66 (s,2H), 4.76 (d, J=6.44 Hz, 2H), 4.80 (s, 2H), 6.98 (m, 3H), 7.08 (m, 4H),7.41 (s, 1H), 7.79 (m, 2H)

Example 620

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (d, J=6.78 Hz, 3H), 0.69 (dd,J=9.16, 6.78 Hz, 3H), 0.80 (d, J=3.39 Hz, 3H), 0.81 (m, 3H), 0.84 (d,J=6.78 Hz, 6H), 1.68 (m, 1H), 1.91 (m, 1H), 2.38 (dd, J=13.05, 11.36 Hz,1H), 2.76 (m, 1H), 2.91 (m, 5H), 2.99 (m, 1H), 3.07 (m, 2H), 3.22 (m,1H), 3.57 (m, 1H), 3.74 (d, J=18.31 Hz, 1H), 3.84 (s, 2H), 4.03 (m, 2H),4.98 (d, J=6.44 Hz, 1H), 6.99 (m, 1H), 7.10 (m, 7H), 7.72 (d, J=8.82 Hz,1H), 8.06 (m, 1H), 8.19 (d, J=9.83 Hz, 1H)

Example 621

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (dd, J=9.16, 6.78 Hz, 6H), 0.81 (m,6H), 0.84 (d, J=6.78 Hz, 6H), 1.68 (m, 1H), 1.92 (m, 2H), 2.38 (dd,J=13.05, 11.36 Hz, 1H), 2.77 (m, 1H), 2.83 (m, 2H), 2.93 (m, 5H), 3.07(m, 2H), 3.21 (dd, J=14.24, 2.71 Hz, 1H), 3.59 (d, J=6.44 Hz, 1H), 3.74(d, J=18.31 Hz, 1H), 3.84 (s, 2H), 4.03 (m, 2H), 4.98 (d, J=6.44 Hz,1H), 7.00 (dd, J=8.99, 4.58 Hz, 1H), 7.10 (m, 7H), 7.72 (d, J=8.82 Hz,2H)

Example 622

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (m, 6H), 0.81 (dd, 2.71 Hz, 6H),1.93 (m, 1H), 2.37 (dd, J=13.22, 11.19 Hz, 1H), 2.79 (m, 1H), 2.83 (s,3H), 2.93 (m, 1H), 3.05 (s, 3H), 3.08 (m, 1H), 3.21 (dd, J=14.24, 3.05Hz, 1H), 3.59 (t, J=6.44 Hz, 1H), 3.73 (d, J=18.31 Hz, 1H), 3.84 (s,3H), 3.91 (d, J=9.49 Hz, 1H), 3.99 (d, J=10.85 Hz, 1H), 4.31 (m, 2H),7.00 (m, 1H), 7.11 (m, 7H), 7.71 (m, 2H), 8.21 (d, J=9.49 Hz, 1H)

Example 623

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (t, J=6.78 Hz, 6H), 0.81 (dd,J=6.61, 2.88 Hz, 6H), 1.93 (m, 2H), 2.37 (dd, J=13.05, 11.36 Hz, 1H),2.80 (dd, J=13.56, 6.44 Hz, 1H), 2.94 (m, 3H), 3.07 (dd, J=13.05, 2.88Hz, 1H), 3.21 (dd, J=14.24, 3.05 Hz, 1H), 3.43 (d, J=4.41 Hz, 2H), 3.57(m, J=3.73 Hz, 4H), 3.63 (d, J=4.41 Hz, 2H), 3.74 (d, J=17.97 Hz, 1H),3.84 (s, 3H), 3.91 (d, J=9.83 Hz, 1H), 3.99 (d, J=11.19 Hz, 1H), 4.35(m, 2H), 7.00 (m, 1H), 7.11 (m, 7 H), 7.72 (d, J=8.82 Hz, 2H), 8.21 (d,J=9.49 Hz, 1H)

Example 624

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (d, J=6.44 Hz, 3H), 0.73 (d, J=6.44Hz, 3H), 0.81 (dd, J=6.44, 3.73 Hz, 6H), 1.94 (m, 2H), 2.40 (dd,J=13.22, 11.19 Hz, 1H), 2.80 (dd, J=13.56, 6.44 Hz, 1H), 2.93 (m, 2H),3.06 (m, 2H), 3.22 (dd, J=14.07, 3.22 Hz, 1H), 3.58 (m, 1H), 3.82 (m,1H), 3.84 (s, 3H), 3.91 (m, 1H), 4.01 (d, J=10.85 Hz, 1H), 4.27 (m, 2H),4.99 (d, J=6.44 Hz, 1H), 7.01 (m, 1H), 7.10 (m, 8H), 7.32 (t, J=7.80 Hz,2H), 7.56 (d, J=7.46 Hz, 2H), 7.71 (m, 2H)

Example 650

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.70 (dd, J=6.61, 4.58 Hz, 6H), 0.80(dd, J=6.61, 4.58 Hz, 6H), 1.94 (m, 2H), 2.42 (dd, J=13.56, 11.19 Hz,1H), 2.63 (s, 3H), 2.71 (m, 1H), 2.83 (m, 2H), 3.00 (m, 3H), 3.18 (m,2H), 3.61 (m, 1H), 3.76 (d, J=10.85 Hz, 1H), 3.92 (m, 1H), 4.33 (d,J=1.36 Hz, 2H), 4.86 (d, J=6.10 Hz, 1H), 5.94 (s, 2H), 6.60 (d, J=8.82Hz, 2H), 7.07 (m, 5H), 7.21 (d, J=3.73 Hz, 1H), 7.39 (d, J=8.82 Hz, 2H),7.84 (d, J=9.49 Hz, 1H)

Example 651

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (dd, J=9.32, 6.61 Hz, 6H), 0.82(dd, J=6.78, 1.36 Hz, 6H), 1.94 (m, 2H), 2.42 (dd, J=13.56, 10.85 Hz,1H), 2.63 (d, J=2.37 Hz, 3H), 2.84 (m, 2H), 2.98 (m, 3H), 3.13 (m, 1H),3.22 (dd, J=14.58, 3.39 Hz, 1H), 3.59 (d, J=5.76 Hz, 1H), 3.75 (d,J=10.51 Hz, 1H), 3.91 (m, 1H), 4.34 (m, 3H), 4.95 (d, J=6.10 Hz, 1H),5.81 (s, 2H), 6.86 (d, J=2.03 Hz, 1H), 6.89 (d, J=2.37 Hz, 1H), 7.06 (m,6H), 7.36 (d, J=8.48 Hz, 1H), 7.85 (d, J=9.49 Hz, 1H)

Example 652

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.90 (m, 6H), 1.87 (m, 1H), 2.13 (m, 1H), 2.65 (m, 1H), 2.69(s, 3H), 2.78 (m, 2H), 2.93 (dd, J=7.63, 2.88 Hz, 2H), 3.04 (d, J=3.39Hz, 2H), 3.10 (m, 1H), 3.16 (dd, J=9.16, 4.07 Hz, 1H), 3.24 (m, 2H),3.59 (d, J=11.19 Hz, 1H), 3.78 (m, 1H), 4.04 (m, 1H), 4.42 (s, 2H), 6.46(d, J=8.82 Hz, 1H), 6.92 (m, 2H), 6.96 (s, 1H), 7.15 (m, 5H), 7.64 (m,2H)

Example 653

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (d, J=6.78 Hz, 3H), 0.70 (d, J=6.78Hz, 3H), 0.79 (d, J=3.39 Hz, 3H), 0.81 (d, J=3.39 Hz, 3H), 1.32 (m, 6H),1.93 (m, 2H), 2.40 (dd, J=13.39, 11.02 Hz, 1H), 2.77 (dd, J=13.73, 6.61Hz, 2H), 2.88 (m, 3H), 2.99 (m, 2H), 3.15 (m, 1H), 3.23 (m, 1H), 3.60(m, 1H), 3.75 (d, J=10.85 Hz, 1H), 3.88 (m, 1H), 4.02 (s, 1H), 4.35 (m,2H), 4.91 (d, J=6.44 Hz, 1H), 6.88 (d, J=8.82 Hz, 2H), 7.06 (m, 6H),7.59 (d, J=8.82 Hz, 2H), 7.85 (d, J=9.49 Hz, 1H)

Example 654

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.70 (t, J=6.27 Hz, 6H), 0.80 (dd,J=6.44, 4.41 Hz, 6H), 1.32 (m, 6H), 1.93 (m, 2H), 2.41 (dd, J=13.56,10.85 Hz, 1H), 2.71 (m, 1H), 2.83 (m, 2H), 3.01 (m, 2H), 3.17 (m, 2H),3.60 (m, 1H), 3.76 (d, J=10.85 Hz, 1H), 3.89 (d, J=10.51 Hz, 1H), 4.02(s, 1H), 4.35 (m, 2H), 4.87 (d, J=6.10 Hz, 1H), 5.94 (s, 2H), 6.60 (d,J=8.82 Hz, 2 H), 7.03 (s, 1H), 7.08 (m, 5H), 7.38 (m, 2H), 7.83 (d,J=9.49 Hz, 1H)

Example 655

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (d, J=6.78 Hz, 3H), 0.70 (m, 3H),0.83 (m, 6H), 1.33 (m, 6H), 1.96 (s, 1H), 2.45 (s, 1H), 2.83 (m, 2H),3.00 (m, 4H), 3.22 (m, 4H), 3.75 (d, J=10.85 Hz, 1H), 3.92 (s, 2H), 4.35(m, 2H), 4.99 (m, 1H), 5.81 (s, 1H), 6.86 (d, J=2.03 Hz, 1H), 6.89 (m,1H), 7.05 (m, 5H), 7.21 (s, 1H), 7.23 (m, 1H), 7.35 (d, J=8.48 Hz, 1H),7.84 (d, J=9.83 Hz, 1H)

Example 656

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.90 (dd, J=8.48, 6.78 Hz, 6H), 1.38 (t, J=7.29 Hz, 3H), 1.68(s, 2H), 1.87 (m, 2H), 2.12 (s, 1H), 2.70 (d, J=14.92 Hz, 1H), 2.83 (s,1H), 2.93 (dd, J=7.29, 4.58 Hz, 3H), 3.04 (s, 2H), 3.11 (d, J=8.14 Hz,3H), 3.24 (d, J=8.48 Hz, 2H), 3.58 (s, 1H), 3.77 (s, 1H), 4.06 (s, 1H),4.42 (s, 1H), 6.92 (d, J=8.82 Hz, 2H), 7.00 (s, 1H), 7.15 (m, 5H), 7.65(d, J=8.48 Hz, 2H)

Example 657

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.38 (m, 3H),1.82 (m, 1H), 2.12 (m, 1H), 2.67 (m, 1H), 2.71 (m, 1H), 2.77 (m, 1H),2.94 (m, 1H), 3.00 (m, 2H), 3.17 (m, 2H), 3.24 (d, J=8.82 Hz, 1H), 3.65(d, J=11.19 Hz, 1H), 3.74 (m, 1H), 3.89 (m, 1H), 4.12 (s, 2H), 4.18 (m,1H), 4.43 (m, 2H), 4.52 (d, J=8.14 Hz, 1H), 4.65 (d, J=10.51 Hz, 1H),6.38 (d, J=9.16 Hz, 1H), 6.67 (m, 2H), 6.95 (s, 1H), 7.15 (m, 5H), 7.57(m, 2H)

Example 658

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.90 (d, J=3.39 Hz, 3H), 0.92 (d, J=3.73 Hz, 3H), 1.37 (t,J=7.63 Hz, 3H), 1.87 (m, 1H), 2.17 (m, 1H), 2.65 (q, J=8.36 Hz, 1H),2.78 (dd, J=14.24, 10.51 Hz, 1H), 2.90 (dd, J=7.46, 4.41 Hz, 2H), 3.00(m, 2H), 3.12 (m, 2H), 3.23 (m, 1H), 3.72 (d, J=3.73 Hz, 1H), 3.76 (d,J=10.17 Hz, 1H), 3.83 (m, 1H), 4.24 (m, 1H), 4.42 (m, 2H), 4.57 (d,J=6.78 Hz, 2H), 6.58 (d, J=8.82 Hz, 1H), 6.94 (s, 1H), 7.01 (d, J=2.03Hz, 1H), 7.04 (t, J=2.54 Hz, 1H), 7.17 (m, 7H), 7.35 (m, 1H)

Example 659

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.90 (m, 3H), 0.93 (d, J=3.05 Hz, 3H), 1.38 (t, J=7.63 Hz, 3H),1.88 (m, 1H), 2.13 (m, 1H), 2.74 (m, 2H), 2.79 (m, 1H), 2.94 (m, 1H),3.01 (m, 2H), 3.05 (d, J=4.07 Hz, 2H), 3.14 (m, 1H), 3.23 (m, 2H), 3.62(m, 1H), 3.77 (m, 2H), 4.06 (m, 1H), 4.43 (d, J=2.37 Hz, 2H), 6.42 (d,Hz, 1H), 6.81 (d, J=8.48 Hz, 1H), 6.98 (s, 1H), 7.01 (d, J=2.37 Hz, 1H),7.04 (d, J=2.37 Hz, 1H), 7.11 (d, J=2.03 Hz, 2H), 7.15 (m, 5H)

Example 660

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.44Hz, 3H), 0.90 (m, 6H), 1.86 (m, 1H), 2.11 (m, 1H), 2.69 (dd, J=14.24,10.17 Hz, 1H), 2.79 (m, 1H), 2.93 (m, 1H), 3.03 (m, 2H), 3.12 (m, 3H),3.23 (m, 2H), 3.48 (s, 3H), 3.61 (d, J=10.85 Hz, 1H), 3.77 (m, 2H), 4.11(m, 1H), 4.47 (m, 2H), 4.70 (s, 2H), 6.51 (d, J=9.16 Hz, 1H), 6.92 (m,2H), 7.12 (s, 1H), 7.17 (m, 5H), 7.65 (m, 2H)

Example 661

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.86 (m, 3H), 0.92 (d,J=6.44 Hz, 3H), 1.82 (dd, J=8.31, 6.61 Hz, 1H), 2.13 (m, 1H), 2.71 (m,2H), 2.77 (m, 1H), 2.93 (m, 1H), 2.97 (m, 2H), 3.11 (m, 4H), 3.21 (m,1H), 3.48 (d, J=3.73 Hz, 3H), 3.65 (d, J=10.85 Hz, 1H), 3.74 (d, J=12.55Hz, 1H), 4.17 (m, 2H), 4.45 (q, J=15.26 Hz, 2H), 4.70 (s, 2H), 6.39 (d,J=8.82 Hz, 1H), 6.67 (m, 2H), 7.09 (d, J=3.73 Hz, 1H), 7.16 (m, 5H),7.56 (m, 2H)

Example 662

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.90 (d, J=3.39 Hz, 3H), 0.92 (d, J=3.39 Hz, 3H), 1.85 (m, 1H),2.18 (m, 1H), 2.67 (q, J=8.48 Hz, 1H), 2.79 (dd, J=14.41, 10.34 Hz, 1H),2.90 (dd, J=7.46, 3.73 Hz, 2H), 3.04 (m, 1H), 3.14 (m, 2H), 3.23 (m,1H), 3.48 (s, 3H), 3.72 (d, J=4.07 Hz, 1H), 3.76 (d, J=10.17 Hz, 1H),3.82 (m, 1H), 4.25 (m, 1H), 4.45 (m, 2H), 4.57 (s, 2H), 4.70 (s, 2H),6.58 (d, J=8.48 Hz, 1H), 7.01 (d, J=2.37 Hz, 1H), 7.03 (d, J=2.03 Hz,1H), 7.09 (s, 1H), 7.19 (m, 6H), 7.35 (m, 1H)

Example 663

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.90 (d, J=3.05 Hz, 3H), 0.93 (d, J=3.39 Hz, 3H), 1.26 (t,J=7.12 Hz, 3H), 1.87 (s, 1H), 2.13 (s, 1H), 2.71 (s, 1H), 2.81 (d,J=13.90 Hz, 2H), 2.92 (t, J=7.12 Hz, 2H), 3.07 (m, 3H), 3.21 (m, 2H),3.49 (s, 3H), 3.64 (d, J=10.51 Hz, 1H), 3.77 (s, 1H), 4.12 (q, J=7.12Hz, 2H), 4.46 (s, 2H), 4.70 (s, 2H), 6.39 (s, 1H), 6.81 (d, J=8.48 Hz,1H), 7.02 (m, 1H), 7.13 (s, 1H), 7.17 (m, 5H)

Example 664

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (dd, J=6.44, 1.70 Hz, 6H), 0.87 (d,J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 2.01 (m, 1H), 2.46 (s, 1H),2.52 (m, 1H), 2.68 (d, J=7.46 Hz, 1H), 2.71 (s, 3H), 2.91 (m, 1H), 2.99(m, 2H), 3.11 (m, 4H), 3.21 (m, 2H), 3.43 (dd, J=14.92, 3.73 Hz, 1H),3.71 (s, 1H), 3.72 (d, J=2.71 Hz, 3H), 3.78 (d, J=11.19 Hz, 1H), 4.12(s, 1H), 4.44 (m, 2H), 6.88 (d, J=8.48 Hz, 1H), 7.08 (m, 3H), 7.16 (m,2H), 7.22 (s, 1H), 7.43 (dd, J=8.48, 2.37 Hz, 1H), 7.68 (d, J=1.36 Hz,1H), 7.75 (s, 1H), 7.81 (d, J=2.37 Hz, 1H), 7.91 (d, J=9.49 Hz, 1H)

Example 665

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.91 (m, 3H), 1.88 (d, J=7.46 Hz, 1H),2.17 (d, J=11.53 Hz, 1H), 2.69 (s, 3H), 2.74 (m, 1H), 2.84 (m, 2H), 2.96(m, 3H), 3.15 (m, 5H), 3.63 (d, J=11.19 Hz, 1H), 3.77 (s, 1H), 4.16 (s,1H), 4.40 (d, J=2.37 Hz, 2H), 6.56 (d, J=9.16 Hz, 1H), 6.93 (s, 1H),7.18 (m, 5H), 7.71 (d, J=3.73 Hz, 1H), 8.02 (s, 1H)

Example 666

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=6.62 Hz, 6H), 0.86 (t, J=6.62Hz, 3H), 0.90 (m, 3H), 1.29 (s, 1H), 2.02 (d, J=6.62 Hz, 1H), 2.47 (dd,J=13.42, 11.21 Hz, 1H), 2.87 (dd, J=13.97, 6.99 Hz, 2H), 2.95 (m, 2H),3.03 (m, 2H), 3.07 (m, 2H), 3.18 (s, 2H), 3.37 (m, 1H), 3.70 (m, 1H),3.75 (s, 1H), 4.14 (s, 1H), 4.31 (d, J=6.62 Hz, 2H), 4.55 (s, 1H), 6.91(m, 1H), 7.03 (m, 3H), 7.14 (m, 2H), 7.32 (m, 1H), 7.67 (m, 2H), 7.92(s, 1H)

Example 667

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (m, 6H), 0.87 (m, 3H), 0.91 (d,J=6.78 Hz, 3H), 1.02 (t, J=7.29 Hz, 1H), 2.03 (m, 1H), 2.52 (m, 1H),2.71 (m, 3H), 2.71 (m, 2H), 2.91 (m, 2H), 3.01 (m, 2H), 3.09 (m, 1H),3.20 (m, 2H), 3.41 (dd, J=14.75, 3.56 Hz, 1H), 3.73 (m, 1H), 3.78 (m,1H), 4.13 (s, 1H), 4.42 (m, 2H), 6.81 (m, 1H), 7.08 (m, 3H), 7.16 (m,2H), 7.23 (m, 1H), 7.48 (m, 1H), 7.54 (dd, J=8.14, 5.76 Hz, 1H), 7.85(t, J=2.71 Hz, 1H), 7.96 (d, J=9.83 Hz, 1H), 8.16 (m, 2H), 8.71 (dd,J=4.92, 1.53 Hz, 1H), 8.88 (d, J=2.37 Hz, 1H)

Example 668

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.78 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 2.02 (m, 2H), 2.51 (m, 2H), 2.70 (s,3H), 2.93 (dd, J=13.39, 7.29 Hz, 2H), 2.98 (s, 3H), 3.07 (m, 3H), 3.14(m, 2H), 3.22 (m, 2H), 3.42 (dd, J=14.75, 3.56 Hz, 1H), 3.73 (m, 1H),3.75 (m, 1H), 4.10 (s, 1H), 4.41 (d, J=7.12 Hz, 2H), 7.01 (m, 1H), 7.08(m, 3H), 7.16 (m, 2H), 7.21 (s, 1H), 7.52 (m, 1H), 7.82 (m, 1H), 7.91(d, J=9.49 Hz, 1H)

Example 669

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.79 (d, J=6.44Hz, 3H), 0.88 (m, 3H), 0.92 (d, J=6.44 Hz, 3H), 0.99 (m, 2H), 1.12 (m,2H), 1.27 (m, 1H), 1.86 (dd, J=13.56, 6.78 Hz, 1H), 2.10 (m, 1H), 2.30(m, 1H), 2.69 (m, 2H), 2.93 (m, 2H), 3.06 (dd, J=661, 3.56 Hz, 2H), 3.13(m, 3H), 3.23 (m, 2H), 3.62 (d, J=10.85 Hz, 1H), 3.78 (m, 2H), 4.09 (m,1H), 4.38 (s, 2H), 6.57 (d, J=9.16 Hz, 1H), 6.88 (m, 1H), 6.93 (m, 1H),7.14 (m, 5H), 7.65 (m, 1H)

Example 670

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.90 (d, J=4.07 Hz, 3H), 0.92 (d, J=4.07 Hz, 3H), 0.99 (m, 3H),1.11 (m, 2H), 1.86 (dd, J=13.39, 6.95 Hz, 1H), 2.17 (m, 1H), 2.28 (m,1H), 2.64 (q, J=8.48 Hz, 1H), 2.78 (dd, J=14.24, 10.51 Hz, 1H), 2.89 (m,2H), 3.04 (dd, J=15.26, 8.14 Hz, 1H), 3.12 (m, 3H), 3.22 (m, 1H), 3.74(m, 2H), 4.26 (m, 1H), 4.38 (m, 2H), 4.57 (s, 1H), 6.55 (d, J=9.16 Hz,1H), 6.83 (s, 1H), 7.02 (dd, J=8.48, 2.03 Hz, 1H), 7.17 (m, 7H), 7.35(d, P8.48 Hz, 1H)

Example 671

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.00 (m, 2H),1.11 (m, 3H), 1.82 (m, 1H), 2.13 (m, 1H), 2.29 (m, 1H), 2.68 (m, 1H),2.75 (m, 2H), 2.96 (m, 2H), 3.10 (m, 4H), 3.21 (m, 1H), 3.65 (d, J=10.85Hz, 1H), 3.74 (s, 1H), 3.89 (s, 1H), 4.16 (m, 2H), 4.38 (m, 2H), 6.38(d, J=8.82 Hz, 1H), 6.68 (m, 2H), 6.84 (s, 1H), 7.16 (m, 5H), 3.56 (m,2H)

Example 672

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.23 (t,J=7.63 Hz, 3H), 1.86 (m, 1H), 2.12 (m, 1H), 2.64 (d, J=7.80 Hz, 1H),2.69 (m, 3H), 2.76 (m, 2H), 2.87 (m, 1H), 2.97 (m, 1H), 3.04 (m, 2H),3.11 (dd, J=8.48, 3.73 Hz, 2H), 3.21 (m, 3H), 3.60 (d, J=10.85 Hz, 1H),3.76 (m, 1H), 4.05 (m, 1H), 4.41 (s, 2H), 6.35 (d, J=9.16 Hz, 1H), 6.84(m, 1H), 6.95 (m, 1H), 7.16 (m, 6H), 7.47 (dd, J=8.48, 2.37 Hz, 1H),7.56 (d, J=2.37 Hz, 1H)

Example 673

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.85 (m, 9H),1.87 (s, 1H), 2.22 (s, 1H), 2.69 (s, 3H), 2.76 (s, 1H), 3.00 (m, 5H),3.23 (m, 3H), 3.32 (s, 2H), 3.60 (d, J=10.51 Hz, 1H), 3.85 (s, 1H), 4.18(s, 1H), 4.43 (m, 2H), 6.80 (s, 1H), 6.92 (d, J=8.48 Hz, 1H), 7.19 (m,5H), 7.52 (d, J=2.03 Hz, 1H), 7.56 (d, J=2.37 Hz, 1H)

Example 674

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.79 (d, J=6.78Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.88 (s, 1H),2.12 (m, 1H), 2.28 (s, 3H), 2.69 (s, 3H), 2.75 (m, 1H), 2.92 (m, 2H),3.14 (m, 4H), 3.60 (d, J=10.85 Hz, 1H), 3.76 (d, J=8.48 Hz, 1H), 4.06(s, 1H), 4.42 (s, 2H), 6.43 (d, J=8.48 Hz, 1H), 6.86 (d, J=8.48 Hz, 1H),6.95 (s, 1H), 7.16 (m, 5H), 7.47 (m, 2H), 7.55 (d, P1.70 Hz, 2H), 7.75(d, J=8.82 Hz, 1H), 7.85 (s, 1H)

Example 675

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.88 (d,J=6.78 Hz, 1H), 2.14 (m, 1H), 2.69 (s, 3H), 2.75 (m, 2H), 2.92 (m, 2H),3.00 (m, 2H), 3.10 (s, 3H), 3.13 (m, 1H), 3.22 (m, 2H), 3.65 (d, J=10.85Hz, 1H), 3.78 (d, J=9.83 Hz, 2H), 4.12 (q, J=7.12 Hz, 1H), 4.42 (m, 2H),6.53 (d, J=8.82 Hz, 1H), 6.93 (s, 1H), 7.15 (m, 5H), 7.33 (d, J=8.82 Hz,2H), 7.57 (s, 1H), 7.77 (d, J=8.82 Hz, 2H)

Example 676

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.88 (m, 3H), 1.88 (m, 1H), 2.16 (m,1H), 2.49 (s, 3H), 2.67 (m, 2H), 2.71 (m, 3H), 2.89 (m, 1H), 3.00 (dd,J=14.24, 4.41 Hz, 1H), 3.14 (d, J=7.46 Hz, 2H), 3.22 (m, 4H), 3.49 (s,1H), 3.58 (d, J=11.19 Hz, 1H), 3.67 (d, J=6.44 Hz, 1H), 3.95 (s, 1H),4.42 (m, 2H), 6.39 (d, J=8.14 Hz, 1H), 6.87 (d, J=8.14 Hz, 1H), 6.97 (s,1H), 7.17 (m, 5H), 7.24 (s, 1H), 7.67 (d, J=10.85 Hz, 1H)

Example 677

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (dd, J=10.85, 6.44 Hz, 9H), 0.88 (m,3H), 1.86 (d, J=6.78 Hz, 1H), 2.17 (m, 1H), 2.51 (s, 3H), 2.68 (d,J=3.73 Hz, 3H), 2.68 (m, 1H), 2.84 (s, 1H), 3.04 (m, 1H), 3.11 (m, 2H),3.19 (m, 2H), 3.25 (m, 2H), 3.49 (d, J=5.09 Hz, 1H), 3.61 (d, J=10.85Hz, 1H), 3.72 (s, 1H), 3.82 (d, J=3.39 Hz, 1H), 4.02 (s, 1H), 4.41 (d,J=1.70 Hz, 2H), 6.44 (d, J=8.82 Hz, 1H), 6.60 (s, 1H), 6.92 (m, 1H),7.17 (m, 5H), 7.91 (s, 1H)

Example 678

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.83 (m, 3H),0.88 (d, J=6.78 Hz, 3H), 0.93 (m, 3H), 1.85 (dd, J=8.48, 6.78 Hz, 1H),2.15 (m, 1H), 2.34 (s, 3H), 2.69 (s, 3H), 2.74 (m, 1H), 2.83 (m, 1H),2.97 (m, 2H), 3.09 (m, 2H), 3.15 (m, 1H), 3.22 (m, 2H), 3.64 (d, J=11.19Hz, 1H), 3.74 (dd, J=8.65, 2.88 Hz, 1H), 3.89 (d, J=3.05 Hz, 1H), 4.16(m, 1H), 4.41 (m, 2H), 6.11 (s, 1H), 6.46 (d, J=8.82 Hz, 1H), 6.92 (d,J=6.44 Hz, 1H), 7.17 (m, 5H), 7.48 (d, J=1.70 Hz, 1H), 7.64 (d, J=2.37Hz, 1H)

Example 679

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (d, J=6.78 Hz, 6H), 0.90 (m, 6H),2.01 (m, 2H), 2.46 (m, 1H), 2.51 (m, 1H), 2.63 (d, J=3.39 Hz, 3H), 2.69(m, 3H), 2.92 (dd, J=13.56, 7.12 Hz, 2H), 3.01 (m, 2H), 3.08 (m, 2H),3.15 (m, 1H), 3.21 (m, 2H), 3.30 (dd, J=3.05, 1.70 Hz, 2H), 3.42 (dd,J=14.92, 3.73 Hz, 1H), 3.74 (m, 2H), 4.11 (m, 1H), 4.41 (s, 2H), 6.94(d, J=8.48 Hz, 1H), 7.09 (m, 3H), 7.15 (m, 2H), 7.20 (s, 1H), 7.42 (dd,8.65, 2.20 Hz, 1H), 7.84 (d, J=2.37 Hz, 1H)

Example 680

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.78, 1.36 Hz, 6H), 0.89 (d,J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.32 (m, 3H), 2.01 (m, 2H),2.51 (m, 2H), 2.69 (s, 3H), 2.93 (m, 1H), 2.97 (m, 1H), 3.06 (m, 2H),3.15 (m, 1H), 3.22 (m, 2H), 3.29 (m, 2H), 3.46 (dd, J=14.92, 3.39 Hz,1H), 3.73 (m, 2H), 4.10 (m, 1H), 4.26 (q, J=7.12 Hz, 2H), 4.41 (m, 2H),6.94 (d, J=8.48 Hz, 1H), 7.09 (m, 3H), 7.15 (m, 2H), 7.18 (s, 1H), 7.38(dd, J=8.48, 2.37 Hz, 1H), 7.91 (m, 1H), 8.34 (d, J=1.70 Hz, 1H)

Example 681

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.25 (d,J=6.78 Hz, 6H), 1.62 (s, 1H), 1.86 (d, J=6.10 Hz, 1H), 2.14 (d, J=6.78Hz, 1H), 2.72 (s, 3H), 2.80 (d, J=18.65 Hz, 1H), 2.89 (m, 1H), 2.96 (m,2H), 3.02 (m, 2H), 3.11 (m, 2H), 3.17 (d, J=9.16 Hz, 1H), 3.26 (m, 2H),3.57 (d, J=11.19 Hz, 1H), 3.77 (d, J=5.43 Hz, 1H), 3.99 (s, 1H), 4.43(s, 2H), 6.30 (d, J=8.82 Hz, 1H), 6.84 (d, J=8.48 Hz, 1H), 6.99 (s, 1H),7.18 (m, 5H), 7.46 (dd, J=8.31, 2.20 Hz, 1H), 7.60 (d, J=2.37 Hz, 1H)

Example 682

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.78 (d, J=6.44Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 0.91 (d, J=2.37 Hz, 3H), 1.88 (dd,J=14.41, 6.95 Hz, 1H), 2.13 (m, 1H), 2.74 (m, 1H), 2.89 (d, J=7.80 Hz,1H), 2.95 (m, 2H), 3.00 (m, 2H), 3.05 (dd, J=6.44, 2.71 Hz, 2H), 3.17(m, 1H), 3.25 (m, 1H), 3.56 (d, J=10.85 Hz, 1H), 3.74 (s, 1H), 3.82 (s,3H), 3.96 (s, 1H), 3.99 (d, J=2.37 Hz, 1H), 4.65 (m, 2H), 6.42 (d,J=8.48 Hz, 1H), 6.95 (d, J=8.82 Hz, 2H), 7.12 (m, 5H), 7.33 (m, 3H),7.63 (d, J=8.82 Hz, 2H), 7.73 (m, 1H)

Example 683

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (m, 3H),0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.85 (d, J=6.78 Hz,1H), 2.13 (m, 1H), 2.29 (s, 6H), 2.70 (s, 3H), 2.73 (d, J=3.05 Hz, 1H),2.79 (m, 1H), 2.96 (d, J=8.14 Hz, 1H), 3.02 (d, J=1.36 Hz, 1H), 3.15 (m,7H), 3.63 (d, J=10.85 Hz, 1H), 3.74 (m, 1H), 4.16 (d, J=9.16 Hz, 1H),4.41 (m, 2 H), 6.38 (d, J=9.49 Hz, 1H), 6.94 (s, 1H), 7.16 (m, 5H), 7.41(d, J=10.17 Hz, 2H)

Example 684

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (dd, J=6.44, 4.41 Hz, 6H), 0.91 (d,J=3.05 Hz, 3H), 0.93 (d, J=3.39 Hz, 3H), 1.55 (s, 1H), 1.87 (s, 1H),2.19 (s, 1H), 2.81 (s, 1H), 2.90 (d, J=7.12 Hz, 2H), 3.05 (s, 2H), 3.15(s, 4H), 3.81 (s, 2H), 4.17 (s, 1H), 4.28 (s, 2H), 4.38 (s, 1H), 6.52(s, 1H), 7.03 (s, 1H), 7.22 (m, 7H), 7.35 (m, 2H), 7.80 (d, J=1.70 Hz,1H)

Example 685

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.90 (m, 6H), 1.84 (m, 1H), 2.16 (m, 1H), 2.73 (dd, J=14.41,10.34 Hz, 1H), 2.86 (m, 3H), 3.07 (dd, J=9.66, 3.22 Hz, 2H), 3.16 (m,1H), 3.24 (m, 1H), 3.31 (t, J=8.99 Hz, 1H), 3.62 (d, J=10.85 Hz, 1H),3.82 (s, 2H), 4.18 (s, 1H), 4.41 (d, J=15.94 Hz, 1H), 4.59 (m, 1H), 6.50(d, J=8.82 Hz, 1H), 6.93 (m, 2H), 7.18 (m, 6H), 7.51 (s, 1H), 7.66 (d,J=8.82 Hz, 2H)

Example 686

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.61 Hz, 6H), 0.90 (d, J=6.44Hz, 3H), 0.97 (d, J=6.78 Hz, 3H), 1.91 (m, 1H), 2.21 (m, 1H), 2.66 (m,2H), 2.70 (s, 3H), 2.84 (m, 2H), 2.94 (d, J=8.48 Hz, 1H), 3.05 (m, 1H),3.13 (m, 1H), 3.20 (m, 1H), 3.28 (m, 1H), 3.39 (s, 1H), 3.93 (d, J=9.16Hz, 2H), 4.32 (m, 1H), 4.45 (m, 2H), 6.67 (d, J=7.12 Hz, 1H), 6.70 (d,J=8.14 Hz, 1H), 6.96 (d, J=3.05 Hz, 1H), 7.14 (m, 3H), 7.19 (m, 7H)

Example 687

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.90 (d, J=3.39 Hz, 3H), 0.92 (d, J=3.05 Hz, 3H), 1.86 (m, 1H),2.14 (s, 3H), 2.67 (m, 1H), 2.79 (dd, J=14.41, 10.68 Hz, 1H), 2.90 (dd,J=7.46, 4.07 Hz, 2H), 3.04 (dd, J=15.26, 8.14 Hz, 1H), 3.11 (dd, J=8.99,4.24 Hz, 3H), 3.16 (m, 3H), 3.23 (m, 2H), 3.77 (d, J=10.17 Hz, 1H), 3.83(m, 1H), 4.25 (m, 1H), 4.45 (m, 2H), 5.34 (s, 2H), 6.57 (d, J=8.48 Hz,1H), 7.01 (d, J=2.03 Hz, 1H), 7.03 (d, J=2.37 Hz, 1H), 7.14 (s, 1H),7.18 (m, 5H), 7.35 (m, 1H)

Example 688

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.78 Hz, 6H), 0.89 (m, 3H),0.92 (d, J=6.44 Hz, 3H), 2.01 (m, 2H), 2.50 (m, 2H), 2.67 (d, J=1.70 Hz,1H), 2.69 (s, 3H), 2.78 (m, 1H), 2.85 (d, J=3.73 Hz, 3H), 2.90 (m, 1H),2.98 (m, 2H), 3.04 (m, 1H), 3.11 (m, 1H), 3.20 (m, 2H), 3.37 (m, 1H),3.71 (m, 1H), 3.77 (m, 1H), 4.13 (m, 1H), 4.42 (s, 2H), 6.75 (d, J=8.14Hz, 1H), 6.85 (d, J=2.37 Hz, 1H), 6.98 (dd, J=8.14, 2.37 Hz, 1H), 7.07(m, 3H), 7.15 (m, 2H), 7.19 (s, 1H)

Example 689

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.27 Hz, 6H), 0.87 (d, J=6.78Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 2.02 (m, 2H), 2.50 (m, 2H), 2.69 (s,3H), 2.76 (s, 6H), 2.91 (dd, J=13.73, 6.95 Hz, 1H), 2.99 (m, 1H), 3.04(m, 1H), 3.11 (m, 1H), 3.17 (m, 1H), 3.23 (m, 2H), 3.34 (d, J=2.37 Hz,1H), 3.37 (m, 1H), 3.71 (d, J=11.19 Hz, 1H), 3.77 (m, 1H), 4.13 (m, 1H),4.42 (s, 2H), 6.90 (m, 1H), 7.08 (m, 3H), 7.15 (m, 2H), 7.19 (s, 1H),7.37 (m, 2H)

Example 690

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.61, 2.20 Hz, 6H), 0.91 (dd,J=9.49, 6.44 Hz, 6H), 1.16 (t, J=7.29 Hz, 3H), 2.03 (m, 1H), 2.50 (m,1H), 2.70 (s, 3H), 2.94 (m, 1H), 3.12 (m, 2H), 3.28 (m, 9H), 3.46 (dd,J=15.09, 3.56 Hz, 1H), 3.75 (d, J=11.19 Hz, 2H), 4.09 (s, 1H), 4.40 (m,2H), 6.90 (d, J=8.48 Hz, 1H), 7.07 (m, 3H), 7.16 (m, 2H), 7.19 (d,J=4.07 Hz, 1H), 7.30 (dd, J=8.48, 2.37 Hz, 1H), 7.99 (d, J=9.49 Hz, 1H),8.45 (m, 1H)

Example 691

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.61, 1.53 Hz, 6H), 0.89 (d,J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 2.02 (m, 1H), 2.51 (m, 1H),2.70 (s, 3H), 2.94 (dd, J=13.90, 7.12 Hz, 2H), 3.11 (m, 4H), 3.21 (m,3H), 3.46 (dd, J=14.75, 3.22 Hz, 1H), 3.77 (m, 3H), 3.79 (m, 3H), 4.08(m, 1H), 4.42 (m, 2H), 6.94 (d, J=8.48 Hz, 1H), 7.08 (m, 3H), 7.15 (m,2H), 7.20 (s, 1H), 7.39 (dd, J=8.48, 2.37 Hz, 1H), 7.90 (d, J=9.49 Hz,1H), 8.34 (s, 1H)

Example 692

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (d, J=6.78 Hz, 6H), 0.89 (d, J=6.44Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 2.02 (m, 1H), 2.47 (m, 1H), 2.50 (m,2H), 2.69 (s, 3H), 2.94 (dd, J=14.07, 6.61 Hz, 2H), 3.05 (m, 2H), 3.14(m, 1H), 3.20 (m, 1H), 3.48 (dd, J=15.09, 3.22 Hz, 1H), 3.75 (m, 2H),4.12 (m, 1H), 4.41 (m, 2H), 5.27 (s, 2H), 6.95 (d, J=8.48 Hz, 1H), 7.07(m, 3H), 7.14 (dd, J=5.93, 3.90 Hz, 2H), 7.17 (s, 1H), 7.31 (m, 1H),7.37 (m, 6H), 7.44 (m, 1H), 7.89 (d, J=9.49 Hz, 1H)

Example 693

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.83 (dd,J=8.14, 6.78 Hz, 1H), 2.14 (m, 1H), 2.26 (s, 3H), 2.69 (s, 3H), 2.72 (m,2H), 2.79 (m, 1H), 2.97 (m, 1H), 3.03 (m, 1H), 3.10 (m, 2H), 3.17 (m,2H), 3.26 (m, 2H), 3.64 (d, J=10.85 Hz, 1H), 3.75 (m, 1H), 3.92 (d,J=3.05 Hz, 1H), 4.17 (m, 3H), 4.41 (m, 2H), 6.43 (d, J=8.82 Hz, 1H),6.92 (d, J=6.44 Hz, 1H), 7.14 (dd, J=8.82, 4.07 Hz, 1H), 7.19 (m, 5H),7.60 (d, J=3.39 Hz, 1H), 7.63 (s, 1H)

Example 694

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=5.09 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.92 (d,J=7.46 Hz, 1H), 2.21 (d, J=5.09 Hz, 3H), 2.69 (s, 3H), 2.74 (d, J=10.51Hz, 1H), 2.93 (m, 2H), 3.25 (m, 6H), 3.49 (s, 1H), 3.56 (d, J=11.19 Hz,1H), 3.70 (d, J=5.43 Hz, 2H), 4.09 (s, 1H), 4.43 (m, 2H), 6.21 (d,J=7.80 Hz, 1H), 6.85 (s, 1H), 6.99 (s, 1H), 7.10 (m, 2H), 7.19 (m, 3H),7.85 (s, 1H)

Example 695

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.27 (M, 1H),1.87 (m, 1H), 2.15 (m, 1H), 2.68 (d, J=4.07 Hz, 3H), 2.72 (s, 3H), 3.08(m, 1H), 3.12 (m, 1H), 3.19 (m, 2H), 3.26 (m, 1H), 3.38 (m, 1H), 3.40(m, 1H), 3.62 (m, 1H), 3.64 (m, 1H), 3.78 (m, 2H), 4.17 (m, 1H), 4.41(m, 2H), 4.47 (s, 1H), 6.54 (d, J=8.82 Hz, 1H), 7.08 (m, 1H), 7.17 (m,5H), 7.86 (m, 1H), 8.24 (d, J=2.37 Hz, 1H)

Example 696

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=3.39 Hz, 3H), 0.83 (d, J=3.73Hz, 3H), 0.91 (d, J=3.73 Hz, 3H), 0.93 (d, J=4.07 Hz, 3H), 1.91 (dd,J=13.39, 6.61 Hz, 1H), 2.18 (m, 1H), 2.69 (s, 3H), 2.75 (m, 1H), 2.83(d, J=8.48 Hz, 1H), 2.90 (dd, J=7.46, 2.37 Hz, 2H), 3.11 (dd, J=14.24,4.07 Hz, 1H), 3.18 (m, 2H), 3.25 (m, 2H), 3.68 (d, P10.85 Hz, 1H), 3.86(m, 2H), 4.10 (s, 1H), 4.41 (s, 2H), 5.61 (d, J=4.75 Hz, 2H), 6.51 (d,J=8.82 Hz, 1H), 6.92 (d, J=6.78 Hz, 1H), 7.18 (m, 5H), 7.54 (s, 1H)

Example 697

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.44 Hz, 3H), 0.78 (d, J=6.78Hz, 3H), 0.91 (t, J=6.27 Hz, 6H), 1.86 (t, J=6.78 Hz, 1H), 2.17 (s, 1H),2.29 (s, 3H), 2.87 (m, 6H), 3.10 (m, 4H), 3.49 (s, 1H), 3.68 (d, J=10.85Hz, 1H), 3.90 (m, 1H), 4.21 (s, 1H), 4.39 (d, J=15.26 Hz, 1H), 4.62 (m,1H), 6.71 (d, J=8.82 Hz, 1H), 6.98 (d, J=8.48 Hz, 1H), 7.16 (m, 2H),7.42 (m, 2H), 7.51 (m, 1H), 7.55 (s, 1H), 7.60 (m, 1H), 7.76 (m, 2H),7.84 (d, J=8.14 Hz, 2H), 8.10 (d, J=1.36 Hz, 1H), 8.17 (d, J=8.82 Hz,1H)

Example 698

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd, J=8.14, 6.78 Hz, 6H), 0.89 (d,J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.84 (d, J=1.70 Hz, 1H), 2.16(m, 1H), 2.29 (s, 3H), 2.76 (dd, J=14.07, 10.00 Hz, 1H), 2.84 (m, 2H),2.94 (m, 2H), 3.04 (m, 1H), 3.13 (m, 3H), 3.65 (d, J=10.85 Hz, 1H), 3.79(s, 1H), 4.15 (d, J=15.26 Hz, 1H), 4.19 (m, 1H), 4.42 (d, J=15.60 Hz,1H), 6.06 (s, 1H), 6.33 (d, J=9.16 Hz, 1H), 6.85 (d, J=8.14 Hz, 1H),7.19 (m, 5H), 7.34 (d, J=1.70 Hz, 1H), 7.50 (dd, J=8.48, 2.37 Hz, 1H),7.56 (d, J=1.70 Hz, 1H), 7.80 (d, J=1.70 Hz, 1H)

Example 699

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (t, J=6.27 Hz, 6H), 0.90 (t, J=7.12Hz, 6H), 1.89 (m, 1H), 2.21 (m, 1H), 2.69 (d, J=8.82 Hz, 1H), 2.82 (m,1H), 2.91 (m, 1H), 3.06 (m, 5H), 3.17 (m, 1H), 3.73 (m, 1H), 3.86 (m,2H), 4.31 (m, 1H), 4.55 (s, 2H), 4.68 (d, J=15.60 Hz, 1H), 4.88 (m, 1H),6.56 (d, J=8.82 Hz, 1H), 7.04 (dd, J=8.48, 2.03 Hz, 1H), 7.15 (m, 5H),7.22 (d, J=2.03 Hz, 1H), 7.28 (s, 1H), 7.36 (d, J=8.14 Hz, 1H), 7.59 (m,1H), 7.75 (m, 1H), 8.02 (s, 1H), 8.11 (d, J=8.48 Hz, 1H), 8.16 (d,J=7.80 Hz, 1H)

Example 700

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.87 (m, 1H),2.13 (m, 1H), 2.69 (s, 3H), 2.74 (m, 1H), 2.88 (dd, J=13.56, 7.12 Hz,2H), 2.94 (m, 2H), 3.02 (m, 1H), 3.07 (t, J=3.73 Hz, 2H), 3.17 (m, 4H),3.61 (d, J=10.85 Hz, 1H), 3.71 (m, 1H), 3.90 (t, J=6.27 Hz, 2H), 4.05(m, 1H), 4.40 (m, 2H), 6.47 (d, J=8.82 Hz, 1H), 6.92 (d, J=6.44 Hz, 1H),7.16 (m, 5H), 7.38 (d, J=8.48 Hz, 2H), 7.73 (d, J=8.48 Hz, 2H)

Example 701

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.86 (t, J=6.61Hz, 6H), 0.92 (d, J=6.44 Hz, 3H), 1.93 (m, 1H), 2.24 (s, 3H), 2.78 (dd,J=13.39, 6.61 Hz, 1H), 2.86 (m, 1H), 3.17 (m, 1H), 3.32 (dd, J=15.09,3.90 Hz, 1H), 3.84 (d, J=9.16 Hz, 1H), 4.00 (dd, J=7.97, 4.24 Hz, 1H),4.06 (m, 1H), 4.27 (m, 2H), 4.47 (m, 1H), 4.81 (d, J=7.12 Hz, 2H), 6.72(s, 2H), 6.88 (m, 1H), 7.00 (d, J=2.03 Hz, 1H), 7.03 (d, J=2.03 Hz, 1H),7.16 (m, 6H), 7.28 (d, J=2.03 Hz, 2H), 7.32 (s, 1H), 7.34 (d, J=3.39 Hz,1H)

Example 702

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (m, 3H), 0.81 (m, 3H), 0.92 (d,J=3.05 Hz, 6H), 1.92 (s, 1H), 2.15 (s, 1H), 2.73 (s, 3H), 2.79 (s, 2H),3.01 (s, 3H), 3.18 (m, 3H), 3.27 (s, 3H), 3.59 (d, J=10.85 Hz, 1H), 3.80(s, 1H), 4.06 (s, 1H), 4.43 (d, J=20.35 Hz, 2H), 6.57 (s, 1H), 7.01 (s,1H), 7.17 (s, 5H), 7.82 (s, 1H), 8.03 (d, J=2.03 Hz, 1H)

Example 703

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.83 (t, J=7.29Hz, 3H), 0.90 (m, 3H), 0.92 (d, J=4.75 Hz, 3H), 0.97 (m, 1H), 1.30 (m,2H), 1.87 (m, 1H), 1.98 (m, 1H), 2.73 (m, 1H), 2.81 (m, 1H), 2.89 (d,J=7.12 Hz, 2H), 2.93 (d, J=15.26 Hz, 1H), 3.10 (m, 2H), 3.19 (m, 2H),3.78 (s, 3H), 3.87 (d, J=10.17 Hz, 2H), 4.26 (m, 1H), 4.49 (d, J=15.26Hz, 1H), 4.51 (s, 2H), 4.77 (d, J=15.26 Hz, 1H), 6.47 (d, J=8.82 Hz,1H), 7.03 (dd, J=8.48, 2.03 Hz, 1H), 7.12 (m, 1H), 7.19 (m, 5H), 7.30(m, 2H), 7.35 (m, 2H), 7.74 (m, 1H)

Example 704

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.85 (t, J=7.29Hz, 3H), 0.93 (m, 6H), 1.00 (m, 1H), 1.32 (m, 1H), 1.69 (s, 2H), 1.90(m, 2H), 1.98 (m, 1H), 2.77 (m, 1H), 2.89 (m, 2H), 3.08 (m, 2H), 3.16(m, 1H), 3.80 (d, J=3.73 Hz, 1H), 3.85 (dd, J=8.31, 3.90 Hz, 1H), 3.97(d, J=9.83 Hz, 1H), 4.31 (m, 1H), 4.57 (s, 2H), 4.66 (d, J=15.60 Hz,1H), 4.91 (d, J=15.60 Hz, 1H), 6.59 (d, J=8.82 Hz, 1H), 7.05 (m, 1H),7.16 (m, 6H), 7.29 (m, 1H), 7.36 (d, J=8.48 Hz, 1H), 7.60 (t, J=7.29 Hz,1H), 7.76 (t, J=7.12 Hz, 1H), 8.11 (d, J=8.14 Hz, 1H), 8.20 (d, J=8.14Hz, 1H), 8.88 (d, J=4.41 Hz, 1H)

Example 705

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.78 Hz, 3H), 0.84 (d, J=7.46Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 0.99 (m, 1H),1.29 (m, 1H), 1.84 (m, 1H), 2.02 (m, 1H), 2.49 (m, 2H), 2.93 (dd,J=13.73, 6.95 Hz, 1H), 3.03 (m, 2H), 3.11 (m, 2H), 3.19 (dd, J=13.73,3.22 Hz, 1H), 3.41 (dd, J=14.92, 3.73 Hz, 1H), 3.76 (m, 1H), 3.85 (d,J=11.19 Hz, 1H), 4.12 (m, 2H), 4.41 (d, J=14.92 Hz, 1H), 4.57 (m, 1H),6.99 (m, 4H), 7.02 (d, J=2.37 Hz, 1H), 7.14 (m, 2H), 7.23 (d, J=1.36 Hz,1H), 7.26 (d, J=2.03 Hz, 2H), 7.36 (d, J=8.14 Hz, 1H), 7.60 (m, 2H),7.92 (d, J=9.49 Hz, 1H), 8.16 (s, 1H)

Example 706

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (m, 3H), 0.88 (m, 6H), 0.94 (d,J=6.44 Hz, 3H), 1.04 (m, 2H), 1.41 (s, 1H), 1.90 (s, 1H), 2.02 (s, 1H),2.93 (m, 2H), 3.02 (m, 2H), 3.10 (m, 2H), 3.17 (m, 2H), 3.25 (m, 2H),3.42 (dd, J=14.92, 3.73 Hz, 1H), 3.78 (s, 1H), 3.87 (m, 1H), 4.18 (m,1H), 4.53 (d, J=15.60 Hz, 1H), 4.79 (d, J=15.94 Hz, 1H), 7.01 (m, 1H),7.11 (m, 4H), 7.19 (m, 2H), 7.26 (m, 1H), 7.36 (d, J=8.14 Hz, 1H), 7.47(d, J=8.48 Hz, 1H), 7.59 (t, J=6.95 Hz, 1H), 7.77 (m, 1H), 7.93 (d,J=8.14 Hz, 1H), 8.03 (d, J=8.48 Hz, 1H), 8.34 (d, J=8.48 Hz, 1H)

Example 707

¹H NMR (300 MHz, CD₃OD) δ ppm 0.91 (m, 15H), 1.09 (m, 1H), 1.29 (d,J=2.94 Hz, 2H), 2.01 (m, 1H), 2.28 (m, 1H), 2.45 (dd, J=13.60, 11.77 Hz,1H), 2.91 (m, 1H), 2.98 (m, 1H), 3.06 (m, 1H), 3.14 (m, 1H), 3.23 (m,2H), 3.27 (m, 1H), 3.38 (dd, J=14.71, 3.68 Hz, 1H), 3.75 (m, 1H), 4.00(s, 1H), 4.05 (m, 1H), 4.59 (m, 2H), 6.99 (m, 2H), 7.11 (m, 3H), 7.24(m, 1H), 7.35 (m, 1H), 7.57 (d, J=10.66 Hz, 1H), 7.75 (dd, J=7.91, 5.33Hz, 1H), 7.92 (m, 1H), 8.64 (m, 2H), 9.25 (s, 1H)

Example 708

¹H NMR (300 MHz, CD₃OD) δ ppm 0.87 (m, 3H), 0.90 (d, J=6.62 Hz, 3H),0.93 (s, 9H), 1.98 (m, 1H), 2.28 (m, 1H), 2.44 (dd, J=13.79, 11.58 Hz,1H), 2.92 (m, 1H), 2.98 (m, 1H), 3.12 (m, 1H), 3.17 (m, 1H), 3.23 (m,2H), 3.29 (m, 3H), 3.35 (m, 1H), 3.75 (m, 1H), 4.01 (s, 1H), 4.06 (s,1H), 4.58 (s, 1H), 4.81 (s, 2H), 6.73 (m, 2H), 6.99 (m, 1H), 7.11 (m,3H), 7.24 (m, 1H), 7.51 (m, 2H), 7.61 (s, 1H), 7.81 (dd, J=8.27, 5.33Hz, 1H), 7.95 (d, J=9.56 Hz, 1H), 8.70 (m, 1H), 9.27 (s, 1H)

Example 709

¹H NMR (300 MHz, CDCl₃) δ ppm 0.92 (d, J=4.78 Hz, 3H), 0.94 (d, J=4.78Hz, 3H), 0.97 (s, 9H), 1.89 (m, 1H), 2.44 (m, 1H), 2.82 (m, 1H), 2.87(m, 1H), 2.91 (m, 1H), 2.94 (d, J=2.94 Hz, 1H), 2.98 (m, 1H), 3.13 (t,J=5.15 Hz, 2H), 3.18 (m, 2H), 3.25 (m, 1H), 3.49 (s, 2H), 3.77 (d,J=4.04 Hz, 1H), 3.84 (m, 1H), 4.12 (s, 1H), 4.34 (m, 2H), 4.53 (m, 1H),4.67 (s, 1H), 4.70 (s, 2H), 6.40 (d, J=9.19 Hz, 1H), 7.00 (dd, J=8.09,2.21 Hz, 1H), 7.10 (m, 1H), 7.14 (dd, J=8.27, 3.13 Hz, 1H), 7.18 (d,J=2.94 Hz, 4H), 7.20 (s, 1H), 7.35 (d, J=8.46 Hz, 1H)

Example 710

¹H NMR (500 MHz, DMSO-d₆) δ ppm 0.63 (d, J=6.71 Hz, 3H), 0.78 (t, J=7.32Hz, 3H), 0.82 (dd, J=6.41, 3.36 Hz, 6H), 0.90 (m, 1H), 1.26 (m, 1H),1.75 (m, 1H), 1.96 (m, 1H), 2.42 (m, 1H), 2.50 (s, 2H), 2.61 (q, J=8.54Hz, 1H), 2.71 (s, 3H), 2.84 (dd, J=13.43, 6.71 Hz, 1H), 2.99 (m, 2H),3.09 (m, 1H), 3.21 (m, 2H), 3.59 (s, 1H), 3.87 (t, J=11.60 Hz, 1H), 3.92(m, 1H), 4.43 (m, 2H), 4.94 (d, J=6.10 Hz, 1H), 5.80 (s, 2H), 6.87 (d,J=8.54 Hz, 1H), 6.99 (t, J=7.02 Hz, 1H), 7.07 (m, 3H), 7.22 (s, 1H),7.36 (d, J=8.54 Hz, 1H), 7.43 (s, 1H), 7.85 (d, J=9.16 Hz, 1H), 8.03 (s,1H)

Example 711

¹H NMR (300 MHz, CD₃OD) δ ppm 0.71 (d, J=6.44 Hz, 3H), 0.77 (d, J=6.78Hz, 3H), 1.00 (d, J=6.10 Hz, 9H), 2.03 (m, 1H), 2.49 (m, 2H), 2.70 (s,3H), 3.06 (m, 2H), 3.22 (m, 3H), 3.38 (s, 1H), 3.47 (m, 2H), 3.68 (d,J=10.85 Hz, 1H), 3.87 (m, 1H), 4.00 (m, 1H), 4.42 (m, 2H), 7.10 (m, 5H),7.22 (s, 1H), 7.77 (m, 2H), 7.87 (m, 3H), 8.14 (s, 1H)

Example 712

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (m, 6H), 0.81 (d, J=5.43 Hz, 6H),1.95 (m, 2H), 2.40 (m, 1H), 2.57 (m, 1H), 2.63 (s, 3H), 2.91 (q, J=6.78Hz, 4H), 3.02 (d, J=10.17 Hz, 4H), 3.13 (m, 4H), 3.25 (s, 1H), 3.57 (s,1H), 3.76 (d, J=10.85 Hz, 1H), 3.89 (s, 1H), 4.33 (s, 2H), 7.08 (m, 4H),7.22 (s, 1H), 7.78 (d, J=3.05 Hz, 2H), 7.90 (s, 1H), 7.93 (s, 4H), 8.85(s, 1H)

Example 715

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.85 (m, 1H),2.15 (m, 1H), 2.69 (s, 3H), 2.74 (m, 1H), 2.85 (dd, J=13.56, 7.12 Hz,1H), 2.95 (d, J=8.14 Hz, 1H), 3.02 (m, 1H), 3.08 (m, 2H), 3.13 (m, 1H),3.21 (m, 1H), 3.49 (d, J=5.43 Hz, 1H), 3.63 (d, J=11.19 Hz, 1H), 3.75(d, J=9.16 Hz, 2H), 4.17 (d, J=1.70 Hz, 1H), 4.41 (m, 2H), 6.50 (d,J=9.16 Hz, 1H), 6.93 (s, 1H), 7.18 (m, 5H), 7.48 (m, 2H), 7.73 (m, 2H)

Example 716

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.85 (s, 1H),2.15 (m, 1H), 2.69 (m, 3H), 2.73 (m, 1H), 2.84 (dd, J=13.56, 6.78 Hz,1H), 2.98 (m, 1H), 3.09 (m, 2H), 3.15 (m, 2H), 3.22 (m, 2H), 3.64 (d,J=10.85 Hz, 1H), 3.76 (m, 1H), 4.17 (s, 1H), 4.42 (m, 2H), 6.49 (d,J=8.82 Hz, 1H), 6.92 (d, J=6.44 Hz, 1H), 7.18 (m, 6H), 7.79 (m, 2H),7.82 (m, 2H)

Example 717

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.87 (d,J=7.46 Hz, 1H), 2.17 (m, 1H), 2.69 (s, 3H), 2.72 (d, J=4.41 Hz, 1H),2.79 (m, 1H), 2.89 (m, 1H), 2.94 (dd, J=12.38, 7.63 Hz, 1H), 3.01 (d,J=7.80 Hz, 1H), 3.08 (m, 1H), 3.13 (m, 2H), 3.19 (m, 2H), 3.24 (m, 1H),3.63 (d, J=10.85 Hz, 1H), 3.77 (s, 1H), 4.16 (s, 1H), 4.41 (m, 2H), 6.56(d, J=8.48 Hz, 1H), 6.92 (m, 1H), 7.19 (m, 5H), 7.56 (dd, J=8.31, 2.20Hz, 1H), 7.75 (m, 1H)

Example 718

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.78 Hz, 3H), 0.85 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 6H), 1.94 (m, 1H), 2.13 (m, 1H), 2.42 (m,3H), 2.64 (m, 1H), 2.69 (d, J=3.39 Hz, 3H), 2.89 (m, 2H), 3.05 (m, 1H),3.14 (m, 2H), 3.20 (m, 1H), 3.39 (dd, J=15.09, 2.20 Hz, 1H), 3.50 (d,J=7.80 Hz, 1H), 3.57 (m, 1H), 3.62 (s, 3H), 3.71 (d, J=10.85 Hz, 1H),3.93 (m, 1H), 4.24 (m, 1H), 4.46 (m, 2H), 6.35 (d, J=9.49 Hz, 1H), 6.95(s, 1H), 7.16 (m, 5H), 7.36 (s, 1H)

Example 719

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 6H), 1.95 (m, 1H), 2.13 (m, 1H), 2.60 (m,1H), 2.68 (m, 1H), 2.69 (s, 3H), 2.92 (dd, J=7.46, 2.03 Hz, 2H), 3.05(m, 1H), 3.12 (m, 2H), 3.20 (m, 1H), 3.41 (dd, J=15.26, 2.37 Hz, 1H),3.51 (m, 1H), 3.77 (s, 3H), 3.92 (s, 1H), 4.24 (dd, J=9.66, 6.27 Hz,1H), 4.44 (m, 2H), 5.98 (s, 1H), 6.41 (d, J=9.83 Hz, 1H), 6.95 (s, 1H),7.12 (m, 5H), 7.46 (d, J=1.36 Hz, 1H), 7.51 (d, J=1.02 Hz, 1H)

Example 720

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.86 (d, J=6.78Hz, 3H), 0.90 (d, J=6.44 Hz, 6H), 1.88 (s, 1H), 2.22 (m, 1H), 2.68 (d,J=5.76 Hz, 3H), 2.75 (m, 1H), 2.90 (d, J=8.82 Hz, 1H), 3.00 (m, 2H),3.26 (m, 6H), 3.60 (d, JA 1.19 Hz, 1H), 3.79 (m, 1H), 4.15 (s, 1H), 4.41(s, 2H), 6.76 (d, J=7.80 Hz, 1H), 6.93 (s, 1H), 7.20 (m, 5H), 8.30 (d,J=2.37 Hz, 1H), 8.69 (d, J=2.03 Hz, 1H)

Example 721

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 2H), 0.85 (t, J=6.27Hz, 6H), 0.89 (d, J=6.44 Hz, 3H), 1.52 (s, 2H), 1.88 (d, J=6.10 Hz, 1H),2.17 (d, J=10.85 Hz, 1H), 2.69 (s, 3H), 2.76 (m, 2H), 2.97 (t, J=7.29Hz, 1H), 3.07 (m, 1H), 3.20 (m, 4H), 3.62 (d, J=10.85 Hz, 1H), 3.73 (d,J=4.07 Hz, 2H), 4.16 (s, 1H), 4.41 (d, J=2.03 Hz, 2H), 6.61 (d, J=8.14Hz, 1H), 6.93 (s, 1H), 7.20 (m, 5H), 7.79 (m, 2H), 7.91 (d, J=8.82 Hz,21-j

Example 722

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (m, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (m, 1H), 2.16 (m,1H), 2.69 (s, 3H), 2.74 (m, 1H), 2.87 (m, 1H), 3.00 (m, 1H), 3.15 (m,4H), 3.25 (m, 1H), 3.64 (d, J=11.19 Hz, 1H), 3.77 (m, 2H), 4.17 (m, 1H),4.41 (m, 2H), 6.51 (d, J=8.82 Hz, 1H), 6.93 (s, 1H), 7.17 (m, 6H), 7.29(m, 1 H), 7.50 (m, 2H), 7.59 (m, 1H)

Example 723

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.16 (m, 1H), 2.68 (d, J=5.09 Hz, 3H), 2.74 (m, 1H), 2.85 (dd, J=13.39,6.95 Hz, 1H), 2.97 (m, 1H), 3.07 (m, 2H), 3.13 (m, 2H), 3.23 (m, 2H),3.64 (d, J=11.19 Hz, 1H), 3.76 (m, 2H), 4.17 (m, 1H), 4.39 (m, 2H), 6.53(d, J=8.48 Hz, 1H), 6.92 (d, J=6.44 Hz, 1H), 7.16 (m, 5H), 7.64 (m, 4H)

Example 724

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (m, 3H), 1.86 (m, 1H), 2.17 (m,1H), 2.69 (s, 3H), 2.76 (m, 1H), 2.94 (dd, J=14.41, 7.63 Hz, 2H), 3.13(m, 2H), 3.23 (m, 2H), 3.64 (d, J=11.19 Hz, 1H), 3.77 (m, 2H), 4.17 (m,1H), 4.41 (m, 2H), 6.58 (d, J=8.48 Hz, 1H), 6.93 (m, 1H), 7.16 (m, 6H),7.69 (m, 2H), 7.88 (dd, J=6.78, 2.37 Hz, 1H), 7.88 (dd, J=6.78, 2.37 Hz,1H)

Example 725

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.85 (dd,J=8.14, 6.78 Hz, 1H), 2.14 (m, 1H), 2.69 (s, 3H), 2.73 (m, 1H), 2.81(dd, J=13.56, 6.78 Hz, 1H), 2.99 (m, 1H), 3.04 (m, 1H), 3.11 (m, 1H),3.20 (m, 4H), 3.64 (d, J=10.85 Hz, 1H), 3.75 (s, 1H), 3.85 (s, 1H), 3.93(s, 3H), 3.94 (s, 3H), 4.18 (m, 1H), 4.41 (m, 2H), 6.43 (d, J=8.82 Hz,1H), 6.92 (d, J=5.76 Hz, 1H), 6.95 (s, 1H), 7.15 (m, 5H), 7.40 (d,J=2.37 Hz, 1H), 7.43 (d, J=2.37 Hz, 1H)

Example 726

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.86 (m, 1H),2.17 (m, 1H), 2.69 (s, 3H), 2.74 (m, 1H), 2.80 (d, J=8.82 Hz, 1H), 2.94(dd, J=13.22, 7.46 Hz, 2H), 3.07 (m, 1H), 3.14 (dd, J=6.44, 3.05 Hz,2H), 3.18 (m, 1H), 3.24 (m, 1H), 3.63 (d, J=11.19 Hz, 1H), 3.76 (m, 2H),4.17 (m, 1H), 4.41 (m, 2H), 6.57 (d, J=8.48 Hz, 1H), 6.93 (s, 1H), 7.17(m, 5H), 7.59 (m, 2H), 7.88 (d, J=2.03 Hz, 1H)

Example 727

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.86 (m, 1H),2.14 (m, 1H), 2.65 (m, 3H), 2.69 (m, 3H), 2.74 (m, 1H), 2.89 (dd,J=13.56, 7.12 Hz, 1H), 3.01 (m, 1H), 3.10 (m, 3H), 3.19 (m, 2H), 3.26(m, 1H), 3.63 (d, J=10.85 Hz, 1H), 3.76 (m, 2H), 4.16 (dd, J=8.82, 5.09Hz, 1H), 4.41 (m, 2H), 6.53 (d, J=8.48 Hz, 1H), 6.92 (d, J=5.76 Hz, 1H),7.17 (m, 5H), 7.88 (m, 2H), 8.06 (m, 2H)

Example 728

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=7.46 Hz, 6H), 0.85 (dd, J=7.12,4.41 Hz, 6H), 1.86 (m, 1H), 2.17 (m, 1H), 2.68 (d, J=3.73 Hz, 3H), 2.77(m, 1H), 3.02 (dd, J=14.07, 4.58 Hz, 1H), 3.19 (m, 5H), 3.43 (m, 2H),3.48 (d, J=4.41 Hz, 1H), 3.61 (d, J=11.19 Hz, 1H), 3.82 (m, 1H), 4.16(m, 1H), 4.41 (m, 2H), 6.56 (d, J=8.48 Hz, 1H), 6.92 (d, J=6.78 Hz, 1H),7.15 (m, 5H), 7.45 (m, 2H)

Example 729

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 6H), 0.86 (m, 6H), 1.86 (d, P6.78Hz, 1H), 2.18 (m, 1H), 2.68 (d, J=5.76 Hz, 3H), 2.80 (m, 1H), 3.04 (dd,J=14.41, 4.58 Hz, 1H), 3.18 (m, 4H), 3.39 (m, 2H), 3.62 (m, 2H), 3.84(d, J=4.07 Hz, 1H), 4.18 (d, J=8.48 Hz, 1H), 4.42 (m, 2H), 6.65 (d,J=8.14 Hz, 1H), 6.94 (s, 1H), 7.18 (m, 5H), 7.65 (m, 1H), 7.70 (dd,J=5.76, 1.70 Hz, 1H), 7.74 (m, 1H), 7.85 (m, 1H), 8.08 (m, 1H)

Example 730

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.78 Hz, 3H), 0.84 (d, J=6.78Hz, 3H), 0.86 (s, 3H), 0.89 (m, 3H), 1.86 (m, 1H), 2.18 (m, 1H), 2.69(s, 3H), 2.75 (m, 1H), 2.86 (m, 1H), 2.96 (m, 2H), 3.07 (m, 1H), 3.20(m, 4H), 3.63 (d, J=10.85 Hz, 1H), 3.76 (m, 2H), 4.18 (d, J=9.16 Hz,1H), 4.41 (m, 2H), 6.63 (d, J=8.48 Hz, 1H), 6.92 (d, J=7.12 Hz, 1H),7.20 (m, 5H), 7.63 (m, 1H), 7.84 (m, 1H), 8.02 (dd, J=9.49, 1.70 Hz,1H), 8.08 (s, 1H)

Example 731

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (t, J=6.44 Hz, 6H), 0.88 (m, 3H),0.90 (m, 3H), 1.89 (m, 1H), 2.18 (m, 1H), 2.68 (d, J=5.76 Hz, 3H), 2.76(m, 1H), 3.08 (m, 3H), 3.16 (dd, J=9.32, 4.58 Hz, 1H), 3.22 (m, 1H),3.29 (m, 2H), 3.49 (d, J=5.43 Hz, 1H), 3.64 (d, J=10.85 Hz, 1H), 3.70(d, J=3.73 Hz, 1H), 3.81 (dd, J=7.63, 4.24 Hz, 1H), 4.19 (m, 1H), 4.41(m, 2H), 6.57 (d, J=8.48 Hz, 1H), 6.92 (d, J=7.46 Hz, 1H), 6.93 (s, 1H),7.16 (m, 5H)

Example 732

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.90 (m, 1H),2.15 (m, 1H), 2.67 (s, 1H), 2.68 (d, J=5.43 Hz, 3H), 2.73 (m, 1H), 2.87(m, 1H), 2.98 (m, 1H), 3.13 (m, 4H), 3.22 (m, 1H), 3.64 (d, J=11.19 Hz,1H), 3.73 (d, J=3.05 Hz, 1H), 3.81 (dd, J=8.48, 4.75 Hz, 1H), 4.18 (d,J=8.82 Hz, 1H), 4.41 (m, 2H), 6.49 (d, J=8.48 Hz, 1H), 6.93 (s, 1H),7.11 (m, 1H), 7.17 (m, 5H), 7.58 (m, 2H)

Example 733

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=3.73 Hz, 3H), 0.83 (m, 6H),0.85 (d, J=6.44 Hz, 3H), 1.81 (d, J=6.44 Hz, 1H), 2.17 (m, 1H), 2.68 (d,J=5.76 Hz, 3H), 2.80 (t, J=8.82 Hz, 1H), 3.03 (dd, J=14.24, 4.41 Hz,1H), 3.19 (m, 5H), 3.35 (d, J=5.43 Hz, 2H), 3.54 (d, J=4.41 Hz, 1H),3.62 (d, J=11.19 Hz, 1H), 3.77 (d, J=5.76 Hz, 1H), 4.15 (s, 1H), 4.39(m, 2H), 6.51 (d, J=8.82 Hz, 1H), 6.92 (d, J=6.44 Hz, 1H), 7.17 (m, 5H),7.37 (dd, 8.65, 2.20 Hz, 1H), 7.51 (d, J=2.03 Hz, 1H), 8.02 (d, J=8.48Hz, 1H)

Example 734

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (dd, J=6.44, 5.09 Hz, 9H), 0.86 (d,J=6.78 Hz, 3H), 1.83 (m, 1H), 2.15 (m, 1H), 2.67 (m, 3H), 2.79 (q,J=8.59 Hz, 1H), 3.02 (dd, J=14.24, 4.41 Hz, 1H), 3.18 (m, 5H), 3.35 (d,J=5.76 Hz, 2H), 3.56 (d, J=4.41 Hz, 1H), 3.61 (m, 1H), 3.78 (m, 1H),4.13 (m, 1H), 4.41 (m, 2H), 6.51 (d, J=8.82 Hz, 1H), 6.92 (d, J=6.44 Hz,1H), 7.17 (m, 5H), 7.34 (t, J=7.97 Hz, 1H), 7.66 (dd, J=8.14, 1.70 Hz,1H), 8.03 (dd, J=7.97, 1.53 Hz, 1H)

Example 735

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.88 (m, 3H), 0.90 (d, J=6.78 Hz, 3H), 1.86 (s, 1H), 2.17 (m,1H), 2.39 (d, J=3.73 Hz, 3H), 2.65 (s, 3H), 2.70 (m, 3H), 2.75 (m, 1H),2.97 (dd, J=14.24, 7.46 Hz, 1H), 3.04 (d, J=5.76 Hz, 1H), 3.10 (m, 1H),3.20 (m, 5H), 3.61 (d, J=10.85 Hz, 1H), 3.68 (d, J=4.07 Hz, 1H), 3.77(s, 1H), 4.14 (s, 1H), 4.41 (m, 2H), 6.56 (d, J=8.82 Hz, 1H), 7.18 (m,6H)

Example 736

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (m, 9H), 0.88 (d, J=6.44 Hz, 3H),1.79 (m, 1H), 2.14 (m, 1H), 2.41 (m, 3H), 2.68 (d, J=6.44 Hz, 3H), 2.69(m, 1H), 2.90 (m, 1H), 3.09 (m, 3H), 3.19 (m, 2H), 3.45 (m, 1H), 3.45(m, 1H), 3.65 (d, J=10.85 Hz, 1H), 3.71 (m, 1H), 3.82 (d, J=3.05 Hz,1H), 3.90 (s, 3H), 4.15 (m, 1H), 4.41 (m, 2H), 6.31 (d, J=9.16 Hz, 1H),6.78 (s, 1H), 6.85 (d, J=8.14 Hz, 1H), 6.93 (s, 1H), 7.13 (m, 5H), 7.79(d, J=8.14 Hz, 1H)

Example 737

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (m, 1H),2.16 (m, 1H), 2.28 (d, J=2.71 Hz, 3H), 2.69 (s, 3H), 2.74 (m, 2H), 2.86(m, 1H), 2.98 (m, 1H), 3.15 (m, 3H), 3.64 (d, J=10.85 Hz, 1H), 3.76 (m,1H), 3.82 (m, 1H), 4.16 (m, 1H), 4.41 (m, 2H), 6.52 (d, J=8.82 Hz, 1H),6.92 (d, J=6.78 Hz, 1H), 7.16 (m, 6H), 7.67 (dd, J=8.82, 2.03 Hz, 1H),7.79 (m, 1H), 7.83 (d, J=2.03 Hz, 1H), 8.61 (d, J=8.82 Hz, 1H)

Example 738

¹H NMR (300 MHz, CDCl₃) δ ppm 0.44 (s, 2H), 0.70 (d, J=6.44 Hz, 3H),0.89 (d, J=6.78 Hz, 3H), 0.99 (d, J=6.44 Hz, 3H), 1.90 (d, 5.60 Hz, 2H),2.37 (d, J=36.28 Hz, 4H), 2.64 (s, 3H), 2.84 (m, 4H), 3.09 (m, 6H), 3.68(s, 1H), 4.17 (s, 2H), 4.45 (d, J=31.87 Hz, 2H), 6.61 (s, 1H), 6.96 (m,6H), 7.67 (s, 1H), 8.39 (s, 1H)

Example 739

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 2H), 0.82 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.92 (m, 3H), 1.89 (d, J=6.44 Hz, 1H),2.16 (d, J=6.78 Hz, 1H), 2.68 (s, 1H), 2.69 (d, J=3.73 Hz, 3H), 2.74 (m,1H), 2.82 (d, J=8.82 Hz, 1H), 2.87 (s, 1H), 2.94 (dd, J=10.68, 7.63 Hz,1H), 3.05 (m, 1H), 3.10 (m, 1H), 3.15 (d, J=6.44 Hz, 1H), 3.22 (m, 1H),3.60 (m, 1H), 3.75 (s, 1H), 3.87 (d, J=3.05 Hz, 1H), 4.08 (d, J=4.75 Hz,1H), 4.41 (s, 2H), 6.49 (d, J=8.48 Hz, 1H), 6.95 (s, 1H), 7.08 (d,J=8.48 Hz, 1H), 7.18 (m, 5H), 7.47 (d, J=1.36 Hz, 1H), 7.51 (m, 1H),7.55 (d, J=2.03 Hz, 1H)

Example 740

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (dd, J=6.61, 3.22 Hz, 6H), 0.81 (dd,J=6.61, 2.54 Hz, 6H), 1.85 (m, 1H), 2.14 (m, 1H), 2.67 (m, 3H), 2.76 (m,1H), 3.03 (m, 1H), 3.16 (m, 5H), 3.33 (m, 2H), 3.60 (d, J=11.19 Hz, 1H),3.70 (d, J=4.07 Hz, 1H), 3.79 (m, 1H), 4.15 (m, 1H), 4.40 (d, J=3.73 Hz,2H), 6.51 (d, J=8.82 Hz, 1H), 6.91 (m, 1H), 7.15 (m, 5H), 7.70 (m, 1H),8.19 (d, J=8.48 Hz, 1H), 8.36 (m, 1H), 8.44 (d, J=6.10 Hz, 1H), 8.70 (d,J=6.10 Hz, 1H), 9.34 (s, 1H)

Example 741

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.86 (dd,J=8.14, 6.78 Hz, 1H), 2.14 (m, 1H), 2.69 (s, 3H), 2.70 (m, 1H), 2.83(dd, J=13.39, 6.61 Hz, 1H), 3.03 (m, 1H), 3.14 (m, 3H), 3.26 (m, 2H),3.62 (d, J=11.19 Hz, 1H), 3.75 (m, 1H), 3.84 (d, J=3.39 Hz, 1H), 3.90(s, 3H), 3.91 (s, 6H), 4.17 (m, 1H), 4.36 (d, J=15.60 Hz, 1H), 4.44 (d,J=15.60 Hz, 1H), 6.45 (d, J=8.82 Hz, 1H), 6.92 (s, 1H), 7.03 (s, 2H),7.17 (m, 5H)

Example 742

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.84 (d,J=8.14 Hz, 1H), 2.15 (m, 1H), 2.44 (d, J=4.41 Hz, 3H), 2.49 (d, J=10.51Hz, 1H), 2.68 (d, J=7.12 Hz, 3H), 2.69 (m, 2H), 2.76 (m, 1H), 2.85 (dd,J=13.56, 6.78 Hz, 1H), 3.00 (m, 1H), 3.11 (m, 3H), 3.21 (m, 2H), 3.64(d, J=11.19 Hz, 1H), 3.78 (m, 1H), 4.16 (m, 1H), 4.41 (m, 1H), 6.48 (d,J=8.82 Hz, 1H), 6.92 (d, J=9.16 Hz, 1H), 7.17 (m, 5H), 7.36 (d, J=7.80Hz, 1H), 7.56 (dd, J=7.97, 1.87 Hz, 1H), 7.77 (d, J=2.03 Hz, 1H)

Example 743

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.78 Hz, 6H), 0.84 (dd, J=6.61,1.53 Hz, 6H), 1.83 (m, 1H), 2.18 (m, 1H), 2.68 (d, J=3.73 Hz, 3H), 2.83(q, J=8.36 Hz, 1H), 3.00 (dd, J=14.41, 4.58 Hz, 1H), 3.19 (m, 6H), 3.41(m, 2H), 3.60 (m, 2H), 3.81 (dd, J=6.95, 4.92 Hz, 1H), 4.15 (m, 1H),4.38 (d, J=16.28 Hz, 2H), 6.58 (d, J=8.14 Hz, 1H), 6.93 (s, 1H), 7.17(m, 6H), 7.62 (m, 1H), 7.72 (m, 1H)

Example 744

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.83 (d, J=4.41 Hz, 3H),0.85 (d, J=3.73 Hz, 3H), 1.85 (m, 1H), 2.17 (m, 1H), 2.69 (m, 3H), 2.83(m, 1H), 3.02 (dd, J=14.41, 4.58 Hz, 1H), 3.19 (m, 4H), 3.38 (d, J=5.76Hz, 2H), 3.55 (d, J=4.41 Hz, 1H), 3.61 (d, J=10.85 Hz, 1H), 3.79 (d,J=5.09 Hz, 1H), 4.15 (s, 1H), 4.41 (s, 2H), 6.55 (d, J=8.48 Hz, 1H),6.93 (s, 1H), 7.16 (m, 5H), 7.23 (d, J=6.10 Hz, 1H), 7.64 (d, J=8.48 Hz,1H), 7.75 (s, 1H), 8.22 (d, J=7.80 Hz, 1H)

Example 745

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (dd, J=9.32, 6.61 Hz, 6H), 0.89 (m,6H), 1.92 (m, 2H), 2.14 (m, 2H), 2.70 (m, 3H), 2.78 (m, 2H), 3.05 (m,4H), 3.21 (m, 3H), 3.78 (d, J=10.85 Hz, 1H), 3.89 (d, J=5.43 Hz, 1H),4.29 (s, 1H), 4.44 (m, 2H), 6.96 (m, 1H), 7.13 (m, 5H), 7.91 (m, 2H),8.14 (d, J=8.82 Hz, 2H)

Example 746

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.15 (m, 1H), 268 (d, J=6.78 Hz, 3H), 2.72 (m, 1H), 2.83 (m, 1H), 2.97(d, J=8.14 Hz, 1H), 3.02 (dd, J=5.59, 2.54 Hz, 1H), 3.08 (dd, J=10.51,3.73 Hz, 1H), 3.14 (s, 1H), 3.17 (m, 1H), 3.24 (m, 1H), 3.64 (d, J=10.85Hz, 1H), 3.76 (m, 1H), 3.83 (d, J=3.39 Hz, 1H), 4.17 (m, 1H), 4.41 (m,2H), 6.45 (d, J=8.82 Hz, 1H), 6.92 (d, J=6.44 Hz, 1H), 7.14 (m, 1H),7.20 (m, 5H), 7.53 (m, 2H), 7.58 (m, 1H), 7.78 (t, J=1.87 Hz, 1H), 7.81(m, 1H)

Example 747

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.85 (d, J=6.44 Hz, 3H),0.87 (d, J=6.44 Hz, 3H), 1.77 (m, 1H), 2.16 (m, 1H), 2.68 (d, J=4.41 Hz,3H), 2.75 (m, 1H), 2.96 (dd, J=14.24, 6.78 Hz, 1H), 3.11 (m, 4H), 3.24(m, 1H), 3.46 (m, 1H), 3.65 (d, J=11.19 Hz, 1H), 3.71 (m, 2H), 3.90 (d,J=3.73 Hz, 3H), 4.08 (m, 1H), 4.15 (m, 1H), 4.41 (m, 2H), 6.41 (d,J=8.82 Hz, 1H), 6.87 (m, 1H), 6.92 (d, J=6.78 Hz, 1H), 7.16 (m, 5H),7.61 (m, 1H), 8.05 (m, 1H)

Example 748

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.78 Hz, 3H), 0.86 (m, 6H),0.90 (m, 3H), 1.91 (m, 1H), 2.16 (m, 1H), 2.67 (s, 3H), 2.77 (dd,J=14.24, 10.17 Hz, 1H), 2.87 (dd, J=13.73, 7.29 Hz, 1H), 2.96 (m, 2H),3.24 (m, 4H), 3.33 (m, 2H), 3.82 (d, J=10.85 Hz, 1H), 3.95 (dd, J=7.97,4.24 Hz, 1H), 4.43 (t, J=4.58 Hz, 1H), 4.48 (m, 2H), 6.92 (s, 1H), 7.09(m, 3H), 7.16 (m, 4H), 7.32 (m, 1H), 7.71 (dd, J=8.14, 1.70 Hz, 1H),7.97 (d, J=1.70 Hz, 1H)

Example 749

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.92 (d, J=6.78 Hz, 3H), 1.85 (m, 1H),2.14 (m, 1H), 2.68 (d, J=5.76 Hz, 3H), 2.73 (m, 1H), 2.83 (dd, J=13.39,6.95 Hz, 1H), 2.99 (m, 1H), 3.08 (m, 1H), 3.15 (d, J=8.14 Hz, 2H), 3.21(m, 2H), 3.64 (d, J=10.85 Hz, 1H), 3.77 (m, 1H), 3.83 (d, J=3.39 Hz,1H), 4.18 (m, 1H), 4.41 (m, 2H), 5.43 (m, 1H), 5.88 (d, J=17.63 Hz, 1H),6.45 (d, J=8.82 Hz, 1H), 6.74 (dd, J=17.63, 10.85 Hz, 1H), 6.93 (s, 1H),7.17 (m, 6H), 7.51 (m, 2H), 7.76 (m, 2H)

Example 750

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.83 (dd,J=8.48, 6.78 Hz, 1H), 2.14 (m, 1H), 2.69 (s, 3H), 2.72 (m, 1H), 2.78 (m,1H), 2.95 (d, J=8.48 Hz, 1H), 3.00 (m, 1H), 3.14 (m, 4H), 3.27 (m, 2H),3.65 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 3.93 (d, J=2.71 Hz, 1H), 4.18(d, J=9.49 Hz, 1H), 4.41 (m, 2H), 4.68 (t, J=8.82 Hz, 2H), 6.41 (d,J=9.49 Hz, 1H), 6.84 (d, J=8.48 Hz, 1H), 6.93 (s, 1H), 7.17 (m, 5H),7.56 (d, J=2.37 Hz, 1H), 7.59 (d, J=2.03 Hz, 1H), 7.61 (s, 1H)

Example 751

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.51 (d,J=6.44 Hz, 3H), 1.89 (m, 1H), 2.15 (m, 1H), 2.69 (m, 3H), 2.74 (m, 1H),2.86 (m, 1H), 3.01 (m, 1H), 3.10 (m, 3H), 3.18 (m, 1H), 3.25 (m, 1H),3.59 (dd, J=10.85, 2.37 Hz, 1H), 3.75 (d, J=9.16 Hz, 2H), 4.09 (dd,J=8.99, 4.24 Hz, 1H), 4.35 (m, 3H), 4.97 (q, J=6.67 Hz, 1H), 6.41 (t,J=8.99 Hz, 1H), 6.92 (s, 1H), 7.15 (m, 5H), 7.53 (d, J=8.48 Hz, 2H),7.76 (d, J=8.48 Hz, 2H)

Example 752

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.15 (m, 1H), 2.69 (s, 3H), 2.71 (m, 2H), 2.80 (m, 1H), 2.99 (m, 3H),3.16 (m, 5H), 3.65 (d, J=10.85 Hz, 1H), 3.75 (m, 1H), 3.87 (s, 1H), 4.16(d, J=14.92 Hz, 1H), 4.41 (m, 2H), 6.08 (s, 2H), 6.46 (d, J=8.82 Hz,1H), 6.90 (m, 2H), 7.17 (m, 5H), 7.35 (dd, J=8.31, 1.86 Hz, 1H)

Example 753

¹H NMR (300 MHz, CDCl₃) δ ppm 0.86 (m, 12H), 1.85 (s, 1H), 2.13 (s, 1H),2.69 (s, 3H), 2.73 (m, 3H), 3.08 (m, 7H), 3.64 (m, 1H), 3.78 (d, J=14.58Hz, 1H), 4.17 (s, 1H), 4.38 (m, 2H), 6.44 (s, 1H), 6.88 (d, J=8.14 Hz,1H), 6.93 (s, 1H), 7.14 (m, 3H), 7.24 (s, 1H), 7.28 (d, J=2.03 Hz, 1H),7.35 (m, 1H), 7.43 (d, J=7.80 Hz, 1H), 7.71 (s, 1H), 7.78 (d, J=2.03 Hz,1H)

Example 754

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.88 (dd, J=7.97, 6.61 Hz, 6H), 1.87 (m, 1H), 2.16 (m, 1H),2.69 (d, J=3.73 Hz, 3H), 2.73 (d, J=4.07 Hz, 1H), 2.81 (m, 1H), 2.97 (m,2H), 3.07 (m, 1H), 3.18 (m, 3H), 3.25 (m, 1H), 3.62 (d, J=10.85 Hz, 1H),3.80 (m, 1H), 4.16 (dd, J=8.99, 4.92 Hz, 1H), 4.42 (m, 2H), 6.62 (d,J=8.48 Hz, 1H), 6.95 (s, 1H), 7.18 (m, 6H), 7.46 (dd, J=7.63, 4.58 Hz,1H), 8.09 (m, 1H), 8.80 (dd, J=4.92, 1.53 Hz, 1H), 9.02 (d, J=1.70 Hz,1H)

Example 755

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.10 Hz, 6H), 0.89 (d, J=6.78Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 1.45 (d, J=6.44 Hz, 9H), 2.02 (m, 1H),2.48 (m, 2H), 2.69 (m, 3H), 2.94 (m, 2H), 3.06 (m, 3H), 3.15 (m, 2H),3.20 (m, 4H), 3.35 (s, 1H), 3.47 (m, 1H), 3.75 (m, 2H), 3.95 (d, J=12.89Hz, 1H), 4.04 (s, 1H), 4.44 (q, J=15.26 Hz, 2H), 6.98 (d, J=8.48 Hz,1H), 7.09 (m, 2H), 7.18 (m, 3H), 7.45 (dd, J=8.48, 2.37 Hz, 1H), 7.94(d, J=9.83 Hz, 1H), 8.53 (d, J=2.03 Hz, 1H)

Example 756

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.44 Hz, 3H), 1.50 (d,J=6.44 Hz, 3H), 1.83 (s, 1H), 2.14 (m, 1H), 2.69 (s, 3H), 2.74 (m, 1H),2.78 (m, 1H), 2.88 (s, 1H), 2.96 (m, 1H), 3.00 (m, 1H), 3.11 (m, 3H),3.21 (m, 1H), 3.35 (m, 1H), 3.65 (d, J=10.85 Hz, 1H), 3.74 (s, 1H), 3.95(d, J=2.71 Hz, 1H), 4.16 (s, 1H), 4.41 (m, 2H), 5.04 (m, 1H), 6.39 (d,J=9.16 Hz, 1H), 6.80 (d, J=8.82 Hz, 1H), 6.93 (s, 1H), 7.17 (m, 5H),7.56 (m, 2H)

Example 757

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.78 Hz, 3H), 0.83 (dd, J=6.78,1.70 Hz, 3H), 0.88 (m, 6H), 1.53 (s, 2H), 1.91 (s, 1H), 2.17 (s, 1H),2.69 (s, 3H), 2.76 (m, 1H), 3.05 (d, J=7.46 Hz, 2H), 3.10 (m, 1H), 3.23(m, 4H), 136 (d, J=3.05 Hz, 1H), 3.62 (d, J=11.53 Hz, 1H), 3.72 (s, 1H),3.88 (s, 1H), 4.17 (s, 1H), 4.39 (m, 2H), 5.20 (d, J=3.73 Hz, 1H), 5.30(s, 1H), 6.54 (s, 1H), 6.69 (d, J=3.39 Hz, 1H), 6.92 (d, J=5.43 Hz, 1H),7.03 (d, J=3.73 Hz, 1H), 7.19 (m, 4H), 7.37 (m, 3H), 7.46 (s, 1H), 8.01(s, 1H)

Example 758

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (m, 3H), 1.87 (m, 1H), 2.14 (m,1H), 2.69 (m, 3H), 2.75 (m, 1H), 2.90 (m, 1H), 3.02 (m, 1H), 3.11 (m,3H), 3.22 (m, 3H), 3.62 (d, J=10.85 Hz, 1H), 3.77 (m, 1H), 3.84 (m, 1H),3.97 (s, 3H), 4.13 (m, 1H), 4.41 (m, 2H), 6.49 (d, J=9.16 Hz, 1H), 6.93(s, 1H), 7.17 (m, 5H), 7.61 (m, 1H), 7.98 (d, J=7.80 Hz, 1H), 8.25 (d,J=7.80 Hz, 1H), 8.44 (d, J=1.70 Hz, 1H)

Example 759

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.87 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 2.65 (m, 3H),2.69 (s, 3H), 2.75 (m, 2H), 2.91 (m, 2H), 3.01 (d, J=7.80 Hz, 1H), 3.10(d, J=19.67 Hz, 2H), 3.21 (m, 1H), 3.27 (m, 3H), 3.62 (d, J=11.19 Hz,2H), 3.78 (d, J=5.76 Hz, 1H), 3.90 (s, 1H), 4.19 (s, 1H), 4.43 (m, 2H),6.54 (s, 1H), 6.93 (s, 1H), 7.19 (m, 4H), 7.63 (m, 1H), 7.99 (d, J=7.80Hz, 1H), 8.15 (m, 1H), 8.36 (s, 1H)

Example 760

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.78 Hz, 3H), 0.88 (m, 9H),1.88 (m, 4H), 2.19 (m, 1H), 2.70 (s, 3H), 2.75 (m, 1H), 2.89 (t, J=7.97Hz, 1H), 3.01 (m, 2H), 3.24 (m, 2H), 3.63 (d, J=10.85 Hz, 1H), 3.77 (dd,J=7.63, 4.24 Hz, 2H), 4.16 (m, 1H), 4.41 (m, 2H), 6.75 (d, J=8.14 Hz,1H), 6.93 (d, J=9.83 Hz, 1H), 7.18 (m, 5H), 7.63 (t, J=5.76 Hz, 2H),8.20 (d, J=6.44 Hz, 2H)

Example 761

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd, J=9.83, 6.78 Hz, 6H), 0.92 (m,3H), 0.96 (d, J=6.78 Hz, 3H), 1.93 (d, J=8.14 Hz, 1H), 2.19 (dd, J=9.16,6.78 Hz, 1H), 2.68 (d, J=9.16 Hz, 3H), 2.77 (m, 2H), 2.89 (m, 2H), 3.11(m, 3H), 3.30 (d, J=7.46 Hz, 2H), 3.39 (m, 1H), 3.88 (m, 2H), 4.29 (s,1H), 4.43 (s, 2H), 6.71 (d, J=8.14 Hz, 1H), 6.96 (s, 1H), 7.07 (m, 1H),7.17 (m, 5H), 7.31 (s, 1H), 7.37 (t, J=7.80 Hz, 1H), 8.95 (s, 1 FD

Example 762

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 3H), 0.84 (d, J=3.39 Hz, 3H),0.87 (m, 6H), 1.91 (d, J=7.46 Hz, 1H), 2.22 (m, 1H), 2.71 (m, 3H), 2.73(m, 1H), 2.89 (t, J=8.65 Hz, 1H), 2.99 (m, 3H), 3.23 (m, 3H), 3.31 (m,2H), 3.62 (d, J=11.19 Hz, 1H), 3.83 (dd, J=6.95, 4.92 Hz, 1H), 4.17 (m,1H), 4.41 (d, J=5.09 Hz, 2H), 6.74 (d, J=8.48 Hz, 1H), 6.93 (m, 2H),7.18 (m, 5H), 7.51 (dd, J=8.82, 2.37 Hz, 1H), 7.73 (d, J=2.37 Hz, 1H)

Example 763

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (m, 3H), 0.82 (d, J=6.78 Hz, 3H),0.90 (m, 3H), 0.94 (dd, J=6.44, 2.37 Hz, 3H), 1.90 (s, 1H), 2.11 (m,1H), 2.69 (d, J=2.03 Hz, 3H), 2.78 (d, J=14.92 Hz, 1H), 2.93 (m, 1H),3.07 (m, 4H), 3.19 (m, 2H), 3.58 (m, 2H), 3.68 (m, 2H), 3.83 (m, 1H),4.01 (s, 1H), 4.36 (m, 2H), 4.89 (m, 1H), 6.35 (d, J=8.82 Hz, 1H), 6.52(d, J=9.16 Hz, 1H), 6.93 (s, 1H), 7.17 (m, 5H), 7.56 (m, 2H), 7.79 (dd,J=8.48, 2.37 Hz, 2H)

Example 764

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.84 (dd,J=10.00, 6.61 Hz, 6H), 0.90 (d, J=6.78 Hz, 3H), 1.86 (m, 1H), 2.16 (m,1H), 2.69 (s, 3H), 2.76 (m, 1H), 2.93 (m, 2H), 3.16 (m, 4H), 3.63 (d,J=11.19 Hz, 1H), 3.77 (s, 2H), 4.12 (q, J=7.12 Hz, 2H), 4.41 (m, 2H),6.55 (d, J=8.14 Hz, 1H), 6.92 (d, J=6.78 Hz, 1H), 7.17 (m, 6H), 7.98 (m,4H), 10.09 (d, J=7.46 Hz, 1H)

Example 765

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.89 (m, 1H),2.14 (m, 1H), 2.69 (d, J=4.75 Hz, 3H), 2.74 (dd, J=15.26, 4.75 Hz, 2H),2.87 (dd, J=13.56, 6.78 Hz, 1H), 3.00 (m, 1H), 3.07 (m, 2H), 3.14 (m,2H), 3.21 (m, 1H), 3.58 (d, J=10.85 Hz, 1H), 3.76 (m, 1H), 4.08 (m, 1H),4.36 (m, 2H), 4.78 (s, 2H), 6.41 (d, J=8.82 Hz, 1H), 6.92 (s, 1H), 7.17(m, 6H), 7.52 (d, J=8.48 Hz, 2H), 7.78 (d, J=8.48 Hz, 2H)

Example 766

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.87 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (s, 1H),2.14 (m, 1H), 2.68 (d, J=4.41 Hz, 3H), 2.75 (m, 2H), 2.85 (dd, J=13.05,6.27 Hz, 1H), 2.98 (m, 1H), 3.16 (m, 4H), 3.63 (d, J=10.85 Hz, 1H), 3.76(s, 1H), 3.85 (s, 1H), 4.12 (dd, J=14.24, 7.12 Hz, 1H), 4.43 (m, 2H),6.50 (s, 1H), 6.94 (s, 1H), 7.16 (m, 6H), 7.58 (m, 1H), 7.75 (m, 4H),8.44 (s, 1H)

Example 767

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.91 (dd, J=6.61, 1.87 Hz, 6H), 1.88 (m, 2H), 2.20 (m, 1H),2.66 (q, J=8.14 Hz, 1H), 2.81 (m, 1H), 2.86 (d, J=7.12 Hz, 1H), 2.93 (d,J=7.80 Hz, 1H), 2.97 (dd, J=8.14, 2.37 Hz, 1H), 3.02 (d, J=8.14 Hz, 1H),3.09 (m, 1H), 3.15 (m, 2H), 3.25 (t, J=7.80 Hz, 2H), 3.79 (d, J=9.49 Hz,1H), 3.85 (m, 1H), 4.27 (t, J=10.00 Hz, 1H), 4.43 (s, 2H), 4.91 (s, 2H),6.73 (d, J=8.82 Hz, 1H), 7.00 (dd, J=8.14, 2.03 Hz, 1H), 7.07 (s, 1H),7.15 (d, J=2.37 Hz, 2H), 7.21 (m, 5H), 7.34 (d, J=8.14 Hz, 1H)

Example 768

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.44, 5.09 Hz, 6H), 0.89 (d,J=6.78 Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 2.02 (m, 1H), 2.21 (s, 3H),2.51 (m, 2H), 2.69 (m, 3H), 2.94 (m, 2H), 3.05 (m, 3H), 3.15 (m, 2H),3.22 (m, 1H), 3.25 (m, 1H), 3.43 (dd, J=14.92, 3.73 Hz, 1H), 3.75 (m,2H), 4.10 (m, 1H), 4.42 (m, 2H), 6.97 (d, J=8.48 Hz, 1H), 7.08 (m, 3H),7.16 (m, 2H), 7.21 (s, 1H), 7.45 (dd, J=8.48, 2.37 Hz, 1H), 7.95 (d,J=9.49 Hz, 1H), 8.38 (d, J=2.37 Hz, 1H)

Example 769

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (m, 6H), 0.89 (d, J=6.44 Hz, 3H),0.93 (d, J=6.78 Hz, 3H), 1.45 (d, J=6.44 Hz, 9H), 2.02 (m, 1H), 2.47(dd, J=13.73, 11.36 Hz, 1H), 2.70 (s, 3H), 2.94 (m, 2H), 3.03 (m, 2H),3.11 (m, 2H), 3.19 (m, 2H), 3.28 (s, 3H), 3.46 (d, J=3.73 Hz, 1H), 3.75(t, J=10.85 Hz, 2H), 3.95 (d, J=12.89 Hz, 1H), 4.03 (s, 1H), 4.44 (q,J=15.60 Hz, 2H), 4.80 (s, 2H), 6.98 (d, J=8.48 Hz, 1H), 7.10 (m, 3H),7.19 (m, 3H), 7.45 (dd, J=8.48, 2.37 Hz, 1H), 7.94 (d, J=9.83 Hz, 1H)

Example 770

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.27 Hz, 6H), 0.89 (d, J=6.78Hz, 3H), 0.92 (d, J=6.44 Hz, 3H), 2.01 (m, 1H), 2.48 (dd, J=13.90, 11.19Hz, 2H), 2.69 (s, 3H), 2.94 (m, 2H), 3.08 (m, 3H), 3.15 (m, 2H), 3.22(d, J=6.44 Hz, 2H), 3.42 (m, 1H), 3.75 (m, 2H), 4.06 (d, J=23.39 Hz,1H), 4.41 (s, 2H), 6.99 (m, 1H), 7.07 (m, 3H), 7.15 (m, 2H), 7.19 (s,1H), 7.45 (dd, J=8.48, 2.37 Hz, 1H), 7.95 (d, J=9.49 Hz, 1H), 8.37 (s,1H), 8.66 (d, J=2.03 Hz, 1H)

Example 771

¹H NMR (300 MHz, CD₃OD) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.76 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 2.00 (m, 1H),2.49 (m, 2H), 2.69 (d, J=5.09 Hz, 3H), 2.93 (dd, J=14.07, 6.95 Hz, 2H),3.04 (m, 2H), 3.10 (s, 1H), 3.12 (m, 2H), 3.21 (m, 2H), 3.34 (s, 1H),3.44 (dd, J=15.09, 3.22 Hz, 1H), 3.74 (m, 1H), 3.82 (s, 1H), 4.07 (m,1H), 4.42 (m, 2H), 6.97 (t, J=8.14 Hz, 1H), 7.07 (m, 3H), 7.13 (m, 2H),7.20 (s, 1H), 7.25 (m, 2H), 7.26 (m, 1H), 7.34 (m, 1H), 7.40 (m, 2H),7.44 (dd, J=8.48, 2.37 Hz, 1H), 7.96 (m, 1H), 8.44 (d, J=2.37 Hz, 1H)

Example 772

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (d, J=3.39 Hz, 3H), 0.78 (m, 3H),0.89 (d, J=6.78 Hz, 3H), 0.92 (m, 3H), 1.42 (s, 9H), 2.03 (m, 2H), 2.49(m, 2H), 2.66 (d, J=6.44 Hz, 2H), 2.70 (s, 3H), 2.95 (m, 2H), 3.01 (s,1H), 3.10 (m, 3H), 3.16 (d, J=4.41 Hz, 3H), 3.43 (t, J=6.61 Hz, 2H),3.49 (s, 1H), 3.74 (m, 2H), 4.08 (s, 1H), 4.42 (s, 2H), 6.98 (d, J=8.48Hz, 1H), 7.08 (m, 3H), 7.15 (m, 2H), 7.20 (s, 1H), 7.45 (dd, J=8.48,2.37 Hz, 1H), 7.94 (d, J=9.49 Hz, 1H), 8.41 (s, 1H)

Example 773

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.86 (d, J=6.78 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.86 (d,J=6.78 Hz, 1H), 2.15 (m, 1H), 2.67 (s, 1H), 2.68 (d, J=4.41 Hz, 3H),2.73 (m, 2H), 2.85 (dd, J=13.56, 7.12 Hz, 1H), 2.99 (m, 1H), 3.06 (dd,J=15.09, 3.22 Hz, 2H), 3.14 (m, 3H), 3.21 (m, 2H), 3.63 (d, J=10.85 Hz,1H), 3.76 (m, 2H), 4.16 (dd, J=9.32, 4.92 Hz, 1H), 4.41 (m, 2H), 6.47(d, J=9.16 Hz, 1H), 6.92 (d, J=6.10 Hz, 1H), 7.16 (m, 5H), 7.71 (d,J=8.48 Hz, 2H), 7.78 (m, 2H), 8.07 (s, 1H)

Example 774

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.86 (m, 3H), 0.94 (d,J=6.44 Hz, 3H), 1.53 (s, 1H), 1.81 (m, 1H), 2.13 (m, 1H), 2.66 (m, 1H),2.69 (s, 3H), 2.75 (m, 1H), 2.96 (m, 2H), 3.08 (m, 4H), 3.17 (m, 2H),3.23 (d, J=8.82 Hz, 1H), 3.65 (m, 1H), 3.68 (d, J=2.71 Hz, 1H), 3.74 (m,1H), 4.00 (d, J=2.71 Hz, 1H), 4.17 (m, 2H), 4.41 (m, 2H), 6.35 (d,J=9.16 Hz, 1H), 6.56 (m, 1H), 6.93 (s, 1H), 7.17 (m, 4H), 7.44 (dd,J=3.90, 2.54 Hz, 2H)

Example 775

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (d, J=6.44 Hz, 6H), 0.91 (d, J=2.71Hz, 3H), 0.93 (d, J=3.05 Hz, 3H), 1.90 (dd, J=13.56, 6.78 Hz, 1H), 2.16(m, 1H), 2.46 (s, 3H), 2.69 (s, 3H), 2.73 (m, 2H), 2.96 (dd, J=7.46,3.39 Hz, 2H), 3.12 (m, 2H), 3.21 (dd, J=8.48, 3.39 Hz, 2H), 3.71 (m,2H), 3.85 (d, J=2.71 Hz, 1H), 4.15 (m, 1H), 4.41 (s, 2H), 5.56 (s, 2H),6.44 (d, J=8.82 Hz, 1H), 6.94 (s, 1H), 7.16 (m, 6H)

Example 776

¹H NMR (300 MHz, CD₃OD) δ ppm 0.76 (t, J=6.61 Hz, 6H), 0.90 (d, J=6.44Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 2.03 (s, 2H), 2.46 (m, 1H), 2.48 (d,J=3.05 Hz, 1H), 2.70 (s, 3H), 2.96 (m, 4H), 3.10 (m, 3H), 3.18 (m, 3H),3.35 (m, 1H), 3.51 (m, 1H), 3.75 (d, J=11.19 Hz, 2H), 4.05 (s, 1H), 4.42(s, 2H), 4.76 (s, 2H), 7.00 (d, J=8.48 Hz, 1H), 7.06 (m, 3H), 7.14 (m,2H), 7.22 (s, 1H), 7.46 (dd, J=8.48, 2.37 Hz, 1H), 7.79 (d, J=9.83 Hz,1H), 8.52 (d, J=2.03 Hz, 1H)

Example 777

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (dd, J=6.78, 2.71 Hz, 6H), 0.91 (m,6H), 1.45 (s, 9H), 2.02 (s, 1H), 2.47 (s, 1H), 2.70 (s, 3H), 3.02 (m,3H), 3.17 (m, 3H), 3.19 (d, J=13.90 Hz, 2H), 3.52 (s, 1H), 3.75 (d,J=10.85 Hz, 1H), 3.91 (s, 1H), 4.08 (s, 1H), 4.47 (m, 2H), 4.72 (d,J=6.10 Hz, 2H), 4.92 (m, 2H), 7.09 (m, 3H), 7.17 (m, 2H), 7.53 (d,J=7.46 Hz, 1H), 7.66 (s, 1H), 7.89 (s, 1H), 8.20 (d, J=1.70 Hz, 1H),8.47 (s, 1H)

Example 778

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.92 (m, 6H), 1.95 (m, 1H), 2.13 (m, 1H), 2.56 (dd, J=14.07,10.68 Hz, 1H), 2.61 (m, 1H), 2.69 (d, J=3.73 Hz, 3H), 3.04 (m, 3H), 3.14(m, 2H), 3.22 (s, 1H), 3.30 (m, 1H), 3.45 (d, J=7.12 Hz, 1H), 3.68 (d,J=10.85 Hz, 1H), 4.07 (m, 1H), 4.36 (d, J=15.26 Hz, 2H), 4.47 (m, 3H),4.74 (m, 1H), 4.85 (m, 1H), 6.94 (s, 1H), 6.98 (d, J=9.16 Hz, 1H), 7.14(m, 5H), 7.51 (m, 1H), 7.69 (m, 1H), 7.93 (s, 1H)

Example 779

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 6H), 1.94 (s, 1H), 2.19 (d, J=10.85 Hz,1H), 2.73 (s, 3H), 2.88 (s, 1H), 3.06 (m, 1H), 3.13 (dd, J=10.51, 7.46Hz, 2H), 3.23 (d, J=1221 Hz, 1H), 3.31 (m, 1H), 3.42 (m, 1H), 3.62 (d,J=10.85 Hz, 1H), 3.87 (s, 1H), 4.12 (q, J=7.12 Hz, 2H), 4.17 (s, 1H),4.43 (s, 2H), 6.70 (d, J=8.82 Hz, 1H), 6.98 (s, 1H), 7.09 (d, J=3.39 Hz,1H), 7.19 (m, 5H), 7.24 (m, 2H), 9.74 (s, 1H)

Example 780

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.91 (dd, J=6.78,4.41 Hz, 6H), 0.96 (d, J=6.44 Hz, 3H), 1.52 (s, 2H), 2.08 (m, 2H), 2.43(m, 1H), 2.69 (d, J=3.73 Hz, 3H), 2.83 (m, 1H), 3.04 (m, 1H), 3.11 (m,1H), 3.14 (m, 3H), 3.24 (m, 1H), 3.30 (m, 1H), 3.62 (s, 1H), 3.92 (d,J=11.19 Hz, 1H), 4.06 (m, 1H), 4.24 (m, 1H), 4.47 (m, 2H), 6.57 (d,J=3.73 Hz, 1H), 6.96 (d, J=3.39 Hz, 1H), 7.13 (m, 5H), 8.05 (s, 1H)

Example 781

¹H NMR (300 MHz, CDCl₃) δ ppm 0.82 (d, J=3.73 Hz, 3H), 0.84 (d, J=3.39Hz, 3H), 0.87 (d, J=4.07 Hz, 3H), 0.89 (d, J=4.07 Hz, 3H), 1.94 (m, 1H),2.17 (m, 1H), 2.65 (m, 1H), 2.69 (m, 3H), 2.76 (m, 1H), 3.05 (dd,J=7.46, 3.39 Hz, 1H), 3.12 (m, 1H), 3.20 (m, 1H), 3.27 (m, 1H), 3.48 (d,J=2.71 Hz, 1H), 3.53 (d, J=4.75 Hz, 1H), 3.67 (d, J=10.85 Hz, 1H), 3.85(s, 1H), 4.12 (q, J=7.12 Hz, 1H), 4.20 (s, 1H), 4.44 (s, 2H), 6.69 (d,J=8.82 Hz, 1H), 6.96 (s, 1H), 7.06 (d, J=3.73 Hz, 2H), 7.12 (m, 2H),7.17 (m, 4H), 7.44 (s, 1H)

Example 782

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.87 (d, J=6.44Hz, 3H), 0.90 (d, J=6.78 Hz, 3H), 1.87 (m, 1H), 2.15 (m, 1H), 2.69 (s,3H), 2.74 (m, 2H), 3.07 (m, 11H), 3.63 (d, J=10.85 Hz, 1H), 3.76 (m,J=20.35 Hz, 2H), 4.12 (m, 1H), 4.39 (d, J=15.60 Hz, 1H), 4.46 (d,J=15.94 Hz, 1H), 4.99 (s, 1H), 6.54 (d, J=8.14 Hz, 1H), 6.94 (s, 1H),7.17 (m, 5H), 7.77 (d, J=8.82 Hz, 2H), 7.81 (d, J=8.82 Hz, 2H)

Example 783

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.44 Hz, 3H), 1.88 (m, 1H),2.14 (m, 1H), 2.68 (m, 3H), 2.75 (m, 1H), 2.96 (dd, J=12.89, 7.12 Hz,2H), 3.09 (m, 4H), 3.23 (m, 3H), 3.61 (d, J=10.85 Hz, 1H), 3.72 (d,J=8.82 Hz, 2H), 4.12 (q, J=7.12 Hz, 1H), 4.41 (m, 2H), 6.52 (d, J=8.82Hz, 1H), 6.93 (s, 1H), 7.18 (m, 6H), 7.87 (d, J=8.48 Hz, 2H), 7.94 (m,2H)

Example 784

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.62 Hz, 3H), 0.85 (dd,J=14.34, 6.99 Hz, 6H), 0.91 (m, 3H), 1.00 (m, 1H), 1.34 (m, 1H), 1.89(dd, J=13.97, 6.99 Hz, 2H), 2.75 (dd, J=14.16, 9.74 Hz, 1H), 2.85 (m,1H), 2.89 (m, 1H), 2.97 (m, 2H), 3.01 (m, 1H), 3.08 (m, 3H), 3.16 (m,2H), 3.75 (d, J=11.03 Hz, 2H), 4.17 (d, J=6.62 Hz, 1H), 4.23 (d, J=15.08Hz, 1H), 4.45 (m, 1H), 6.49 (d, J=8.46 Hz, 1H), 7.19 (m, 5H), 7.29 (d,J=5.15 Hz, 1H), 7.59 (m, 1H), 7.88 (m, 2H), 7.94 (m, 2H), 8.51 (s, 1H),8.55 (d, J=3.31 Hz, 1H)

Example 785

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.62 Hz, 3H), 0.88 (m, 9H),1.00 (m, 1H), 1.36 (m, 1H), 1.87 (m, 1H), 1.97 (m, 1H), 2.78 (m, 1H),2.89 (m, 1H), 2.96 (m, 2H), 3.04 (m, 3H), 3.17 (m, 2H), 3.24 (m, 1H),3.77 (m, 3H), 4.20 (m, 2H), 4.45 (m, 1H), 6.58 (d, J=8.46 Hz, 1H), 7.19(m, 5H), 7.59 (m, 1H), 7.80 (m, 2H), 7.91 (m, 2H), 8.51 (d, J=1.84 Hz,1H), 8.55 (dd, J=4.78, 1.47 Hz, 1H)

Example 787

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.86 (s, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.33 (t, J=7.63 Hz, 3H),1.82 (m, 1H), 2.08 (m, 1H), 2.65 (dd, J=14.07, 10.68 Hz, 1H), 2.76 (dd,J=13.22, 6.44 Hz, 1H), 2.97 (m, 4H), 3.07 (dd, J=13.90, 4.07 Hz, 1H),3.16 (d, J=8.82 Hz, 1H), 3.22 (d, J=17.97 Hz, 1H), 3.58 (d, J=17.97 Hz,1H), 3.80 (m, 1H), 3.83 (d, J=3.73 Hz, 1H), 3.90 (d, J=11.19 Hz, 1H),4.16 (s, 2H), 4.23 (m, 1H), 4.76 (m, 2H), 6.16 (d, J=9.49 Hz, 1H), 6.68(m, 2H), 7.00 (s, 1H), 7.09 (s, 5H), 7.56 (m, 2H)

Example 788

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.10 Hz, 6H), 0.89 (m, 3H),0.94 (d, J=6.44 Hz, 3H), 1.33 (m, 3H), 1.84 (m, 1H), 2.08 (m, 1H), 2.67(dd, J=14.07, 10.68 Hz, 1H), 2.85 (m, 2H), 3.06 (t, J=3.39 Hz, 1H), 3.25(d, J=17.63 Hz, 1H), 3.60 (d, J=17.63 Hz, 1H), 3.64 (s, 1H), 3.87 (m,2H), 3.96 (m, 1H), 4.24 (m, 1H), 4.43 (s, 2H), 4.75 (d, J=6.10 Hz, 2H),4.83 (m, 2H), 6.26 (d, J=9.16 Hz, 1H), 7.01 (s, 1H), 7.03 (t, J=2.54 Hz,1H), 7.06 (t, J=2.37 Hz, 1H), 7.13 (m, 5H), 7.18 (d, J=2.03 Hz, 1H),7.37 (d, J=8.48 Hz, 1H)

Example 789

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (dd, J=6.61, 2.88 Hz, 6H), 0.87 (d,J=6.78 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 2.00 (m, 2H), 2.45 (m, 1H),2.65 (s, 3H), 2.88 (m, 3H), 3.03 (m, 1H), 3.22 (m, 1H), 3.39 (dd,J=14.58, 3.73 Hz, 1H), 3.68 (d, J=18.31 Hz, 1H), 3.77 (m, 1H), 4.00 (d,J=10.85 Hz, 1H), 4.15 (m, 2H), 4.73 (d, J=6.44 Hz, 2H), 6.90 (m, 2H),6.99 (m, 3H), 7.13 (m, 2H), 7.22 (m, 1H), 7.67 (m, 2H), 8.21 (d, J=9.83Hz, 1H)

Example 790

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (m, 6H), 0.89 (d, J=6.78 Hz, 3H),0.94 (d, J=6.44 Hz, 3H), 1.85 (m, 1H), 2.09 (m, 1H), 2.65 (s, 3H), 2.74(d, J=11.87 Hz, 1H), 2.87 (m, 3H), 3.07 (m, 2H), 3.15 (m, 1H), 3.23 (m,1H), 3.59 (m, 1H), 3.83 (m, 1H), 3.92 (m, 2H), 4.23 (m, 1H), 4.43 (s,2H), 4.73 (d, J=6.78 Hz, 2H), 4.80 (d, J=6.44 Hz, 1H), 6.30 (d, J=9.16Hz, 1H), 7.01 (s, 1H), 7.03 (t, J=2.54 Hz, 1H), 7.06 (m, 1H), 7.10 (s,5H), 7.19 (m, 1H), 7.37 (d, J=8.14 Hz, 1H)

Example 791

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (m, 6H), 0.89 (d, J=6.44 Hz, 3H),0.93 (d, J=6.44 Hz, 3H), 1.86 (m, 1H), 2.65 (m, 2H), 2.74 (s, 3H), 2.85(m, 2H), 2.95 (m, 2H), 2.98 (m, 2H), 3.07 (m, 2H), 3.15 (m, 1H), 3.57(d, J=17.97 Hz, 1H), 3.83 (m, 1H), 3.92 (d, J=11.19 Hz, 1H), 4.15 (m,1H), 4.72 (m, 2H), 6.68 (d, J=9.16 Hz, 1H), 6.79 (d, J=8.48 Hz, 1H),7.04 (m, 7 H), 7.14 (d, J=2.37 Hz, 1H)

Example 792

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (t, J=6.95 Hz, 6H), 0.89 (d, J=6.78Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.84 (m, 1H), 2.08 (m, 1H), 2.68 (dd,J=14.24, 10.85 Hz, 1H), 2.84 (m, 1H), 2.98 (m, 1H), 3.18 (m, 1H), 3.27(d, J=17.97 Hz, 1H), 3.44 (s, 3H), 3.48 (d, J=6.10 Hz, 1H), 3.60 (d,J=17.63 Hz, 1H), 3.84 (m, 2H), 3.91 (m, 1H), 4.25 (m, 1H), 4.67 (s, 2H),4.76 (m, 2H), 6.24 (d, J=9.16 Hz, 1H), 7.02 (d, J=2.03 Hz, 1H), 7.05 (d,J=2.37 Hz, 1H), 7.11 (s, 6H), 7.18 (m, 2H), 7.37 (d, J=8.48 Hz, 1H)

Example 793

¹H NMR (300 MHz, CD₃OD) δ ppm 0.78 (dd, J=6.61, 3.90 Hz, 6H), 0.87 (d,J=6.44 Hz, 3H), 0.90 (d, J=6.44 Hz, 3H), 1.99 (m, 2H), 2.46 (dd,J=13.56, 11.87 Hz, 1H), 2.87 (dd, J=13.73, 6.95 Hz, 1H), 3.00 (m, 2H),3.22 (m, 1H), 3.35 (m, 2H) 3.42 (m, 3H), 3.68 (d, J=18.31 Hz, 1H), 3.78(m, 1H), 4.00 (d, J=10.85 Hz, 1H), 4.13 (m, 1H), 4.65 (d, J=5.09 Hz,2H), 4.77 (d, J=5.76 Hz, 2H), 6.90 (m, 2H), 6.99 (q, J=3.50 Hz, 3H),7.12 (m, 2H), 7.41 (s, 1H), 7.65 (m, 2H), 8.20 (d, J=9.49 Hz, 1H)

Example 794

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.86 (s, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.82 (m, 1H), 2.06 (m,1H), 2.65 (dd, J=14.24, 10.85 Hz, 1H), 2.76 (dd, J=13.22, 6.44 Hz, 1H),2.95 (m, 1H), 3.08 (dd, J=13.90, 4.07 Hz, 1H), 3.20 (m, 2H), 3.46 (s,3H), 3.51 (s, 2H), 3.59 (m, 1H), 3.82 (m, 1H), 3.88 (d, J=10.85 Hz, 1H),4.21 (m, 2H), 4.70 (s, 2H), 4.79 (m, 2H), 6.34 (d, J=9.49 Hz, 1H), 6.69(d, J=8.82 Hz, 2H), 7.05 (m, 6H), 7.24 (s, 1H), 7.56 (d, J=8.48 Hz, 2H)

Example 795

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (m, 1H),2.06 (m, 1H), 2.65 (dd, J=14.07, 10.68 Hz, 1H), 2.80 (m, 1H), 2.98 (m,1H), 3.05 (m, 1H), 3.18 (m, 2H), 3.54 (d, J=17.63 Hz, 1H), 3.59 (s, 1H),3.81 (s, 1H), 3.87 (d, J=11.19 Hz, 1H), 4.21 (m, 1H), 4.38 (s, 2H), 4.62(m, 2H), 6.06 (d, J=9.49 Hz, 1H), 7.03 (m, 6H), 7.16 (d, J=2.03 Hz, 1H),7.33 (m, 5H), 7.41 (m, 2H)

Example 796

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (m, 1H),2.06 (m, 1H), 2.33 (s, 3H), 2.64 (dd, J=14.24, 10.51 Hz, 1H), 2.81 (m,1H), 2.98 (m, 1H), 3.05 (m, 2H), 3.18 (m, 2H), 3.54 (d, J=17.97 Hz, 1H),3.59 (s, 1H), 3.84 (s, 1H), 3.88 (d, J=10.85 Hz, 1H), 4.21 (m, 1H), 4.38(s, 2H), 4.58 (d, J=2.03 Hz, 2H), 6.06 (d, J=9.49 Hz, 1H), 7.05 (m, 6H),7.16 (d, J=2.37 Hz, 1H), 7.22 (m, 4H), 7.37 (d, J=8.48 Hz, 1H)

Example 797

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.85 (m, 1H),2.12 (m, 1H), 2.73 (dd, J=14.24, 10.85 Hz, 1H), 2.83 (dd, J=13.56, 6.78Hz, 1H), 2.97 (m, 1H), 3.07 (m, 2H), 3.16 (m, 1H), 3.37 (d, J=17.97 Hz,1H), 3.57 (s, 1H), 3.66 (d, J=17.97 Hz, 1H), 3.86 (m, 1H), 3.93 (d,J=10.51 Hz, 1H), 4.26 (m, 1H), 4.85 (m, 2H), 6.17 (d, J=8.82 Hz, 1H),7.03 (dd, J=8.48, 2.03 Hz, 1H), 7.15 (d, J=4.07 Hz, 5H), 7.35 (t, J=3.90Hz, 2H), 7.39 (m, 1H), 7.56 (m, 2H), 7.66 (d, J=7.80 Hz, 1H)

Example 798

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.90 (m, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.83 (m, 1H), 2.09 (m,1H), 2.69 (dd, J=14.07, 10.68 Hz, 1H), 2.82 (dd, J=13.56, 6.78 Hz, 1H),3.02 (m, 4H), 3.17 (m, 1H), 3.30 (d, J=17.97 Hz, 1H), 3.61 (d, J=17.97Hz, 2H), 3.84 (s, 1H), 3.89 (d, J=10.85 Hz, 1H), 4.26 (m, 1H), 4.70 (m,2H), 6.11 (d, J=9.16 Hz, 1H), 7.03 (dd, J=8.14, 2.03 Hz, 1H), 7.11 (m,5H), 7.15 (d, J=2.37 Hz, 1H), 7.37 (d, J=8.48 Hz, 1H), 7.52 (t, J=7.97Hz, 1H), 7.72 (d, J=7.80 Hz, 1H), 8.15 (d, Hz, 1H), 8.24 (t, J=1.87 Hz,1H)

Example 800

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.95 (d, J=6.44 Hz, 3H), 1.82 (m, 1H),2.07 (m, 1H), 2.65 (dd, J=14.24, 10.85 Hz, 1H), 2.82 (m, 1H), 2.99 (m,2H), 3.06 (m, 1H), 3.19 (m, 1H), 3.53 (s, 1H), 3.60 (d, J=4.41 Hz, 2H),3.82 (m, 1H), 3.87 (d, J=11.19 Hz, 1H), 4.24 (m, 1H), 4.37 (d, J=6.78Hz, 2H), 4.62 (m, 2H), 6.06 (d, J=9.49 Hz, 1H), 7.05 (m, 4H), 7.09 (d,J=1.70 Hz, 1H), 7.14 (s, 1H), 7.17 (d, J=2.37 Hz, 2H), 7.26 (d, J=9.83Hz, 2H), 7.39 (t, J=3.73 Hz, 1H)

Example 801

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.95 (d, J=6.44 Hz, 3H), 1.83 (dd,J=8.31, 6.61 Hz, 1H), 2.07 (m, 1H), 2.67 (dd, J=14.24, 10.85 Hz, 1H),2.82 (dd, J=13.56, 6.78 Hz, 1H), 3.01 (m, 3H), 3.20 (m, 2H), 3.58 (m,2H), 3.82 (m, 1H), 3.87 (d, J=10.85 Hz, 1H), 4.23 (d, J=4.75 Hz, 1H),4.37 (d, J=6.78 Hz, 2H), 4.60 (m, 2H), 6.06 (d, J=9.49 Hz, 1H), 7.04 (m,6H), 7.17 (m, 2H), 7.37 (d, J=8.14 Hz, 1H), 7.44 (m, 2H)

Example 802

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.44 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.84 (m, 1H),2.05 (m, 2H), 2.30 (s, 3H), 2.65 (dd, J=14.24, 10.85 Hz, 1H), 2.81 (m,1H), 3.01 (m, 2H), 3.17 (m, 2H), 3.53 (d, J=17.97 Hz, 1H), 3.60 (d,J=3.05 Hz, 1H), 3.81 (m, 1H), 3.87 (d, J=10.85 Hz, 1H), 4.12 (q, J=7.12Hz, 2H), 4.22 (m, 1H), 4.37 (d, J=6.78 Hz, 2H), 4.57 (m, 2H), 6.07 (d,J=9.49 Hz, 1H), 7.02 (d, J=2.37 Hz, 1H), 7.06 (m, 2H), 7.13 (d, J=7.80Hz, 2H), 7.16 (d, J=2.37 Hz, 1H), 7.30 (d, J=8.14 Hz, 2H), 7.37 (d,J=8.48 Hz, 1H)

Example 803

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.84 (d, J=6.78Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (dd,J=8.14, 6.78 Hz, 1H), 2.09 (m, 1H), 2.70 (dd, J=14.24, 10.85 Hz, 1H),2.82 (m, 1H), 3.01 (m, 3H), 3.16 (m, 1H), 3.32 (d, J=17.97 Hz, 1H), 3.61(m, 1H), 3.62 (m, 1H), 3.84 (m, 1H), 3.89 (d, J=10.85 Hz, 1H), 4.27 (m,1H), 4.37 (d, J=6.78 Hz, 2H), 4.69 (m, 2H), 6.12 (d, J=9.16 Hz, 1H),7.03 (m, 1H), 7.10 (m, 5H), 7.14 (t, J=2.71 Hz, 1H), 7.37 (d, J=8.14 Hz,1H), 7.54 (m, 2H), 8.19 (m, 1H)

Example 804

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (d, J=6.44 Hz, 3H), 0.89 (m, 6H),0.92 (d, J=6.78 Hz, 3H), 1.84 (m, 1H), 2.17 (m, 1H), 2.72 (dd, J=14.07,10.68 Hz, 1H), 2.83 (dd, J=13.22, 6.78 Hz, 1H), 2.96 (m, 1H), 3.08 (m,1H), 3.17 (m, 1H), 3.43 (d, J=17.97 Hz, 1H), 3.76 (m, 2H), 3.85 (m, 1H),3.96 (d, J=10.85 Hz, 1H), 4.27 (m, 1H), 4.40 (s, 1H), 4.98 (m, 2H), 6.26(d, J=9.16 Hz, 1H), 7.03 (dd, J=8.31, 2.20 Hz, 1H), 7.17 (m, 7H), 7.34(t, J=8.14 Hz, 2H), 7.48 (m, 1H), 7.64 (m, 1H), 7.76 (d, J=7.80 Hz, 1H),7.93 (d, J=8.48 Hz, 1H), 8.12 (d, J=8.48 Hz, 1H)

Example 805

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.69 (t, J=7.12 Hz, 3H), 0.75 (d, J=6.78Hz, 3H), 0.81 (t, J=6.10 Hz, 6H), 1.96 (m, 2H), 2.38 (dd, J=13.05, 11.70Hz, 1H), 2.83 (m, 2H), 2.94 (dd, J=8.99, 4.24 Hz, 1H), 3.02 (d, J=18.31Hz, 2H), 3.09 (d, J=3.39 Hz, 1H), 0.00 (none, 1H), 3.59 (s, 1H), 3.88(s, 3H), 3.94 (d, J=7.12 Hz, 1H), 4.02 (d, J=10.85 Hz, 1H), 4.12 (m,1H), 4.93 (d, J=17.29 Hz, 3H), 5.81 (s, 2H), 6.88 (dd, J=8.48, 2.03 Hz,1H), 6.97 (m, 1H), 7.13 (m, 5H), 7.25 (m, 1H), 7.35 (m, 1H), 7.48 (d,J=8.14 Hz, 1H), 7.55 (d, J=7.80 Hz, 1H), 8.23 (d, J=9.83 Hz, 1H)

Example 806

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.09 (m, 1H), 2.66 (dd, J=14.07, 10.68 Hz, 1H), 2.81 (dd, J=13.56, 6.44Hz, 1H), 2.97 (m, 1H), 3.04 (m, 2H), 3.18 (m, 1H), 3.23 (m, 1H), 3.58(m, 2H), 3.82 (m, 1H), 3.89 (d, J=10.85 Hz, 1H), 4.24 (s, 1H), 4.36 (d,J=6.78 Hz, 2H), 4.66 (m, 2H), 6.07 (d, J=9.16 Hz, 1H), 7.02 (m, 1H),7.05 (m, 6H), 7.17 (m, 1H), 7.34 (m, 1H), 7.41 (m, 2H), 7.48 (d, J=8.48Hz, 2H), 7.55 (m, 3H)

Example 807

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.82 (dd,J=15.09, 6.61 Hz, 1H), 2.09 (m, 1H), 2.67 (dd, J=14.24, 10.51 Hz, 1H),2.81 (dd, J=13.39, 6.61 Hz, 1H), 2.98 (m, 1H), 3.05 (m, 1H), 3.19 (m,1H), 3.29 (d, J=17.97 Hz, 1H), 3.61 (m, 2H), 3.84 (m, 1H), 3.89 (d,J=10.85 Hz, 1H), 4.24 (m, 1H), 4.39 (d, J=6.78 Hz, 2H), 4.70 (m, 2H),6.09 (d, J=9.16 Hz, 1H), 7.03 (m, 1H), 7.08 (d, J=1.70 Hz, 5H), 7.17 (d,J=2.03 Hz, 1H), 7.37 (d, J=8.48 Hz, 1H), 7.42 (s, 1H), 7.46 (d, J=7.80Hz, 2H), 7.50 (d, J=8.48 Hz, 2H), 7.58 (m, 1H), 7.74 (m, 2H), 7.78 (d,J=8.48 Hz, 1H)

Example 808

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (d, J=6.78 Hz, 3H), 0.72 (d, J=6.78Hz, 3H), 0.82 (d, J=6.10 Hz, 6H), 0.92 (m, 1H), 1.94 (m, 1H), 2.32 (m,1H), 2.83 (dd, J=13.90, 6.78 Hz, 1H), 2.92 (m, 2H), 3.03 (m, 1H), 3.21(dd, J=14.07, 2.88 Hz, 1H), 3.58 (s, 1H), 3.83 (d, J=17.97 Hz, 1H), 3.92(s, 1H), 4.02 (d, J=10.51 Hz, 1H), 5.00 (d, J=6.44 Hz, 1H), 5.06 (m,2H), 5.81 (s, 2H), 6.81 (m, 3H), 6.87 (m, 1H), 7.00 (m, 2H), 7.22 (d,J=2.03 Hz, 1H), 7.38 (m, 2H), 7.49 (m, 1H), 7.61 (m, 2H), 7.89 (d,J=8.14 Hz, 1H), 7.97 (m, 1H), 8.21 (d, J=9.49 Hz, 1H), 8.38 (d, J=8.48Hz, 1H)

Example 809

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.70 (dd, J=9.16, 6.78 Hz, 6H), 0.82 (m,6H), 1.94 (m, 2H), 2.37 (m, 1H), 2.83 (dd, J=13.73, 6.95 Hz, 1H), 2.93(m, 2H), 3.03 (m, 1H), 3.22 (m, 1H), 3.58 (s, 1H), 3.81 (d, J=18.31 Hz,1H), 3.96 (s, 1H), 4.01 (d, J=10.85 Hz, 1H), 4.77 (d, J=7.46 Hz, 2H),5.00 (d, J=6.44 Hz, 1H), 5.81 (s, 2H), 6.82 (m, 3H), 6.87 (dd, J=8.31,2.20 Hz, 1H), 7.03 (m, 2H), 7.22 (d, J=2.03 Hz, 1H), 7.36 (d, J=8.48 Hz,1H), 7.51 (m, 3H), 7.82 (s, 1H), 7.89 (m, 2H), 7.93 (m, 1H), 8.22 (d,J=9.49 Hz, 1H)

Example 810

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (dd, J=6.61, 2.54 Hz, 3H), 0.82 (dd,J=6.44, 1.70 Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.93 (t, J=6.10 Hz, 3H),1.62 (d, J=6.44 Hz, 2H), 1.85 (m, 1H), 2.07 (m, 1H), 2.66 (dd, J=14.07,10.68 Hz, 1H), 2.81 (m, 1H), 2.97 (dd, J=5.59, 2.54 Hz, 1H), 3.00 (m,3H), 3.20 (m, 2H), 3.52 (d, J=4.07 Hz, 1H), 3.59 (m, 1H), 3.82 (s, 1H),3.87 (d, J=11.19 Hz, 1H), 4.23 (s, 1H), 4.37 (d, J=6.44 Hz, 2H), 4.61(m, 2H), 7.04 (m, 6H), 7.16 (s, 1H), 7.36 (d, J=2.37 Hz, 3H), 7.37 (m,1H), 7.41 (m, 1H)

Example 811

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.86 (m, 1H),2.08 (m, 1H), 2.55 (s, 3H), 2.69 (dd, J=14.24, 10.85 Hz, 1H), 2.82 (dd,J=13.39, 6.61 Hz, 1H), 2.97 (m, 1H), 3.06 (m, 1H), 3.17 (m, 1H), 3.27(d, J=17.97 Hz, 1H), 3.59 (m, 2H), 3.83 (s, 1H), 3.88 (d, J=10.85 Hz,1H), 4.24 (m, 1H), 4.39 (s, 2H), 4.63 (m, 2H), 6.07 (d, J=9.49 Hz, 1H),7.03 (dd, J=8.14, 2.03 Hz, 1H), 7.10 (m, 5H), 7.14 (m, 1H), 7.31 (d,J=7.80 Hz, 1H), 7.37 (m, 1H), 7.52 (dd, J=7.80, 1.70 Hz, 1H), 7.99 (d,J=1.70 Hz, 1H)

Example 812

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (m, 6H), 0.89 (d, J=6.78 Hz, 3H),0.94 (d, J=6.44 Hz, 3H), 1.83 (m, 1H), 2.12 (m, 1H), 2.73 (dd, J=14.24,10.85 Hz, 1H), 2.82 (m, 1H), 3.00 (m, 2H), 3.08 (m, 1H), 3.18 (m, 1H),3.41 (d, J=17.97 Hz, 1H), 3.60 (s, 1H), 3.69 (d, J=17.97 Hz, 1H), 3.84(s, 1H), 3.90 (d, J=10.85 Hz, 1H), 4.29 (m, 1H), 4.38 (s, 1H), 5.04 (m,2H), 6.08 (d, J=9.49 Hz, 1H), 7.03 (dd, J=8.31, 2.20 Hz, 1H), 7.16 (m,7H), 7.37 (d, J=8.14 Hz, 1H), 7.44 (m, 1H), 7.57 (m, 1H), 8.07 (dd,J=8.14, 1.36 Hz, 1H)

Example 813

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (d,J=1.36 Hz, 1H), 2.10 (m, 1H), 2.56 (m, 3H), 2.72 (dd, J=14.41, 10.68 Hz,1H), 2.82 (m, 1H), 2.98 (m, 1H), 3.06 (m, 2H), 3.18 (m, 1H), 3.36 (d,J=18.31 Hz, 1H), 3.63 (m, 2H), 3.86 (s, 1H), 3.88 (d, J=10.85 Hz, 1H),4.27 (d, J=5.76 Hz, 1H), 4.38 (s, 1H), 4.69 (m, 2H), 6.09 (d, J=9.49 Hz,1H), 7.03 (dd, J=8.31, 2.20 Hz, 1H), 7.11 (d, J=7.12 Hz, 5H), 7.15 (d,J=2.03 Hz, 1H), 7.30 (m, 1H), 7.37 (d, J=8.48 Hz, 1H), 7.52 (d, J=7.46Hz, 1H), 7.67 (m, 1H)

Example 814

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.10 (m, 1H), 2.67 (dd, J=13.90, 10.85 Hz, 1H), 2.81 (m, 1H), 2.98 (m,2H), 3.03 (m, 1H), 3.16 (m, 1H), 3.26 (d, J=17.97 Hz, 1H), 3.60 (m, 2H),3.82 (m, 1H), 3.90 (d, J=10.85 Hz, 1H), 4.25 (m, 1H), 4.39 (s, 1H), 4.67(m, 2H), 6.11 (d, J=9.49 Hz, 1H), 7.02 (m, 1H), 7.08 (m, 5H), 7.15 (d,J=2.03 Hz, 1H), 7.24 (s, 1H), 7.35 (d, J=8.14 Hz, 1H), 7.55 (d, J=8.48Hz, 2H), 8.02 (m, 2H)

Example 815

¹H NMR (300 MHz, CD₃OD) δ ppm 0.75 (dd, J=8.48, 6.78 Hz, 6H), 0.89 (m,6H), 1.98 (m, 1H), 2.46 (m, 1H), 2.99 (m, 3H), 3.21 (dd, J=13.90, 3.39Hz, 1H), 3.31 (m, 3H), 3.40 (dd, J=14.92, 3.73 Hz, 1H), 3.69 (d, J=18.31Hz, 1H), 3.78 (m, 1H), 3.98 (m, 1H), 4.13 (m, 1H), 4.67 (m, 2H), 6.88(m, 2H), 6.99 (dd, J=8.31, 2.20 Hz, 1H), 7.09 (m, 2H), 7.23 (m, 2H),7.35 (d, J=8.14 Hz, 1H), 7.45 (dd, J=7.46, 4.41 Hz, 1H), 7.89 (m, 1H),8.49 (m, 1H), 8.62 (d, J=1.70 Hz, 1H)

Example 816

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (m, 6H), 0.90 (m, 6H), 2.02 (m, 2H),2.49 (dd, J=13.56, 11.87 Hz, 1H), 2.92 (m, 1H), 3.03 (m, 2H), 3.11 (d,J=3.05 Hz, 1H), 3.22 (m, 1H), 3.30 (d, J=1.70 Hz, 3H), 3.41 (dd,J=14.92, 3.73 Hz, 1H), 3.78 (m, 2H), 4.00 (d, J=10.85 Hz, 1H), 4.16 (m,1H), 4.55 (s, 1H), 4.73 (m, 1H), 6.98 (d, J=2.03 Hz, 1H), 7.01 (t,J=2.20 Hz, 1H), 7.07 (m, 3H), 7.16 (m, 2H), 7.22 (s, 1H), 7.25 (d,J=2.03 Hz, 1H), 7.30 (dd, J=6.78, 5.43 Hz, 1H), 7.35 (m, 1H), 7.37 (m,1H)

Example 817

¹H NMR (300 MHz, CD₃OD) δ ppm 0.77 (d, J=6.44 Hz, 6H), 0.88 (m, 3H),0.91 (d, J=6.78 Hz, 3H), 2.01 (m, 2H), 2.49 (dd, J=13.73, 11.70 Hz, 1H),2.86 (s, 2H), 2.93 (m, 1H), 2.99 (m, 2H), 3.05 (d, J=9.49 Hz, 2H), 3.11(m, 1H), 3.22 (dd, J=13.73, 3.56 Hz, 1H), 3.41 (dd, J=14.75, 3.90 Hz,1H), 3.77 (m, 2H), 4.00 (d, J=10.85 Hz, 1H), 4.09 (m, 1H), 4.55 (s, 1H),4.72 (d, J=10.17 Hz, 1H), 6.99 (m, 3H), 7.01 (d, J=2.37 Hz, 1H), 7.14(dd, J=6.10, 3.05 Hz, 2

H), 7.22 (d, J=4.41 Hz, 1H), 7.25 (d, J=2.03 Hz, 1H), 7.35 (d, J=8.14Hz, 1H), 7.40 (d, Hz, 2H)

Example 818

¹H NMR (300 MHz, CDCl₃) δ ppm 0.85 (d, J=6.78 Hz, 6H), 0.89 (d, J=6.44Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.84 (m, 1H), 2.14 (m, 1H), 2.74 (dd,J=14.07, 11.02 Hz, 1H), 2.83 (m, 1H), 2.98 (m, 1H), 3.06 (dd, J=10.85,3.73 Hz, 1H), 3.15 (m, 1H), 3.28 (d, J=17.97 Hz, 1H), 3.66 (m, 2H), 3.85(m, 1H), 3.94 (d, J=10.85 Hz, 1H), 3.98 (s, 3H), 4.27 (m, 1H), 4.40 (s,2H), 4.70 (m, 2H), 6.10 (d, J=9.16 Hz, 1H), 6.92 (d, J=9.16 Hz, 1H),7.02 (m, 1H), 7.13 (m, 1H), 7.16 (d, J=7.46 Hz, 6H), 7.36 (d, J=8.48 Hz,1H), 7.93 (d, J=2.71 Hz, 1H), 8.15 (dd, J=8.99, 2.88 Hz, 1H)

Example 819

¹H NMR (300 MHz, CDCl₃) δ ppm 0.73 (d, J=6.78 Hz, 3H), 0.79 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (d,J=6.78 Hz, 1H), 2.04 (m, 1H), 2.71 (dd, J=14.24, 10.51 Hz, 1H), 2.80 (m,1H), 2.98 (m, 1H), 308 (dd, J=14.41, 4.24 Hz, 1H), 3.16 (m, 1H), 3.26(d, J=17.63 Hz, 1H), 3.54 (d, J=17.97 Hz, 1H), 3.62 (d, J=3.05 Hz, 1H),3.82 (d, J=10.85 Hz, 2H), 4.25 (s, 1H), 4.38 (s, 2H), 5.02 (m, 2H), 5.97(d, J=9.49 Hz, 1H), 7.03 (dd, J=8.31, 2.20 Hz, 1H), 7.15 (m, 7H), 7.35(m, 2H), 7.44 (m, 1H), 7.73 (d, J=8.14 Hz, 1H)

Example 820

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.83 (m, 1H),2.08 (m, 1H), 2.58 (s, 3H), 2.69 (dd, J=14.24, 10.51 Hz, 1H), 2.82 (dd,J=13.56, 6.78 Hz, 1H), 2.92 (d, J=21.70 Hz, 1H), 3.04 (m, 1H), 3.17 (m,1H), 3.31 (d, J=17.97 Hz, 1H), 3.57 (s, 1H), 3.62 (m, 1H), 3.83 (dd,J=8.31, 3.22 Hz, 1H), 3.89 (d, J=10.51 Hz, 1H), 4.25 (m, 1H), 4.38 (d,J=6.78 Hz, 2H), 4.62 (m, 2H), 6.11 (d, J=9.49 Hz, 1H), 7.03 (dd, J=8.48,2.03 Hz, 1H), 7.11 (m, 5H), 7.14 (m, 1H), 7.34 (m, 2H), 7.37 (d, J=8.14Hz, 1H), 7.93 (d, J=9.16 Hz, 1H)

Example 821

¹H NMR (300 MHz, CDCl₃) δ ppm 0.76 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.85 (m, 1H),2.06 (m, 1H), 2.64 (dd, J=14.07, 10.68 Hz, 1H), 2.81 (m, 1H), 2.98 (m,1H), 3.05 (m, 1H), 3.18 (m, 2H), 3.37 (s, 3H), 3.55 (d, J=17.97 Hz, 1H),3.60 (s, 1H), 3.79 (s, 1H), 3.87 (d, J=10.85 Hz, 1H), 4.12 (q, J=7.12Hz, 1H), 4.22 (m, 1H), 4.43 (s, 3H), 4.62 (m, 2H), 6.06 (d, J=9.49 Hz,1H), 7.04 (m, 7H), 7.17 (d, J=2.03 Hz, 1H), 7.32 (m, 1H), 7.34 (m, 2H),7.38 (s, 1H)

Example 822

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (dd, J=6.44, 2.03 Hz, 6H), 0.89 (d,J=6.78 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.86 (s, 1H), 2.12 (m, 1H),2.30 (s, 3H), 2.75 (dd, J=14.07, 10.68 Hz, 1H), 2.95 (m, 1H), 3.06 (m,1H), 3.14 (m, 2H), 3.49 (m, 1H), 3.59 (d, J=18.31 Hz, 1H), 3.64 (s, 1H),3.76 (m, 1H), 3.80 (d, J=9.49 Hz, 1H), 3.87 (m, 3H), 3.88 (d, J=4.07 Hz,1H), 4.11 (s, 1H), 4.93 (m, 1H), 6.11 (d, J=8.48 Hz, 1H), 6.87 (d,J=8.48 Hz, 1H), 7.15 (m, 6H), 7.33 (m, 2H), 7.45 (dd, J=8.31, 2.20 Hz,1H), 7.56 (d, J=2.03 Hz, 1H), 7.65 (d, J=7.80 Hz, 1H)

Example 823

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.95 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.07 (m, 1H), 2.66 (dd, J=14.24, 10.85 Hz, 1H), 2.81 (dd, J=13.39, 6.61Hz, 1H), 2.98 (m, 1H), 3.06 (m, 1H), 3.20 (m, 2H), 3.57 (m, 2H), 3.83(m, 1H), 3.88 (d, J=10.85 Hz, 1H), 4.24 (m, 1H), 4.38 (s, 2H), 4.57 (m,2H), 6.05 (d, J=9.49 Hz, 1H), 7.04 (m, 6H), 7.16 (d, J=2.03 Hz, 1H),7.22 (d, J=7.80 Hz, 1H), 7.33 (s, 1H), 7.37 (d, J=8.48 Hz, 1H), 7.43 (d,J=8.14 Hz, 1H), 7.57 (s, 1H)

Example 824

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.81 (m, 1H),2.07 (m, 1H), 2.59 (d, J=5.76 Hz, 3H), 2.66 (m, 1H), 2.82 (dd, J=13.22,6.78 Hz, 1H), 3.01 (m, 2H), 3.17 (m, 1H), 3.22 (m, 1H), 3.58 (d, J=17.97Hz, 1H), 3.62 (d, J=3.05 Hz, 1H), 3.83 (dd, J=8.65, 5.26 Hz, 1H), 3.89(d, J=10.85 Hz, 1H), 4.25 (m, 1H), 4.40 (d, J=6.78 Hz, 2H), 4.68 (m,2H), 6.13 (d, J=9.49 Hz, 1H), 7.04 (m, 6H), 7.16 (d, J=2.37 Hz, 1H),7.37 (d, J=8.14 Hz, 1H), 7.44 (t, J=7.63 Hz, 1H), 7.61 (m, 1H), 7.88 (d,J=7.80 Hz, 1H), 7.99 (s, 1H)

Example 825

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.44 Hz, 3H), 0.82 (d, J=6.78Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.83 (m, 1H),2.07 (m, 1H), 2.63 (dd, J=14.24, 10.85 Hz, 1H), 2.81 (m, 1H), 3.00 (m,2H), 3.19 (m, 2H), 3.58 (m, 2H), 3.82 (m, 1H), 3.90 (d, J=10.85 Hz, 1H),4.21 (s, 1H), 4.39 (d, J=6.78 Hz, 2H), 4.72 (m, 2H), 6.12 (d, J=9.49 Hz,1H), 7.04 (m, 7H), 7.16 (d, J=2.03 Hz, 1H), 7.51 (m, 2H), 7.94 (m, 1H),8.10 (s, 1H), 8.51 (d, J=2.37 Hz, 1H), 8.62 (m, 1H), 9.02 (d, J=1.36 Hz,1H)

Example 826

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (d, J=6.78 Hz, 3H), 1.62 (m, 3H),1.82 (m, 1H), 2.07 (m, 1H), 2.62 (dd, J=14.24, 10.85 Hz, 1H), 2.81 (dd,J=13.56, 6.78 Hz, 1H), 3.18 (m, 2H), 3.56 (d, J=17.97 Hz, 1H), 3.61 (d,J=3.05 Hz, 1H), 3.82 (m, 1H), 3.90 (d, J=10.85 Hz, 1H), 4.22 (m, 1H),4.38 (d, J=6.78 Hz, 2H), 4.65 (m, 2H), 6.10 (d, J=9.49 Hz, 1H), 7.03 (m,8H), 7.18 (m, 1H), 7.31 (m, 2H), 7.36 (m, 2H), 7.53 (m, 1H), 7.66 (s,1H)

Example 827

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.78 Hz, 3H), 0.84 (d, J=6.44Hz, 3H), 0.89 (d, J=6.44 Hz, 3H), 0.94 (d, J=6.44 Hz, 3H), 1.86 (m, 1H),2.08 (m, 1H), 2.70 (dd, J=14.07, 10.68 Hz, 1H), 2.82 (m, 1H), 2.98 (m,2H), 3.05 (m, 2H), 3.18 (m, 1H), 3.32 (d, J=17.97 Hz, 1H), 3.88 (d,J=10.85 Hz, 2H), 4.25 (m, 1H), 4.40 (s, 1H), 4.57 (m, 2H), 6.12 (d,J=9.49 Hz, 1H), 7.03 (dd, J=8.14, 2.03 Hz, 1H), 7.11 (m, 6H), 7.16 (d,J=2.37 Hz, 1H), 7.37 (m, 1H), 7.53 (d, J=1.70 Hz, 1H), 7.94 (d, J=1.70Hz, 1H)

Example 828

¹H NMR (300 MHz, CDCl₃) δ ppm 0.81 (dd, J=8.99, 6.61 Hz, 6H), 0.88 (d,J=6.44 Hz, 3H), 0.95 (d, J=6.44 Hz, 3H), 1.83 (d, J=7.46 Hz, 1H), 2.09(m, 1H), 2.29 (d, J=6.78 Hz, 3H), 2.70 (dd, J=14.24, 10.51 Hz, 1H), 2.78(m, 1H), 2.92 (d, J=2.37 Hz, 1H), 2.99 (m, 2H), 3.08 (m, 1H), 3.20 (m,1H), 3.31 (d, J=17.63 Hz, 1H), 3.61 (d, J=17.97 Hz, 1H), 3.83 (m, 2H),4.24 (s, 1H), 4.66 (m, 2H), 5.60 (s, 1H), 5.94 (s, 2H), 6.05 (d, J=9.49Hz, 1H), 6.85 (m, 1H), 7.14 (s, 5H), 7.51 (dd, J=8.48, 2.37 Hz, 1H),7.55 (s, 1H)

Example 829

¹H NMR (300 MHz, CDCl₃) δ ppm 0.84 (t, J=6.27 Hz, 6H), 0.88 (m, 3H),0.94 (d, J=6.44 Hz, 3H), 1.82 (d, J=8.14 Hz, 1H), 2.11 (s, 1H), 2.71(dd, J=14.07, 10.68 Hz, 1H), 2.82 (m, 1H), 2.97 (m, 1H), 3.05 (m, 2H),3.11 (d, J=4.41 Hz, 1H), 3.19 (m, 2H), 3.40 (d, J=18.31 Hz, 1H), 3.64(s, 1H), 3.71 (d, J=17.97 Hz, 1H), 3.84 (s, 1H), 3.92 (d, J=10.85 Hz,1H), 4.25 (d, J=9.83 Hz, 1H), 5.06 (m, 2H), 6.15 (d, J=9.16 Hz, 1H),7.04 (dd, J=8.31, 2.20 Hz, 1H), 7.16 (m, 5H), 7.37 (m, 1H), 7.44 (m,1H), 7.83 (d, J=8.14 Hz, 1H), 7.97 (d, J=7.46 Hz, 1H)

Example 830

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (m, 6H), 0.88 (d, J=6.78 Hz, 3H),0.95 (d, J=6.78 Hz, 3H), 1.83 (s, 1H), 2.10 (s, 1H), 2.30 (s, 3H), 2.76(m, 2H), 2.91 (m, 1H), 2.98 (m, 2H), 3.06 (s, 1H), 3.18 (d, J=8.48 Hz,1H), 3.41 (d, J=17.97 Hz, 1H), 3.68 (m, 1H), 3.82 (d, J=3.39 Hz, 1H),3.86 (d, J=10.85 Hz, 1H), 4.28 (s, 1H), 5.00 (m, 2H), 6.08 (m, 2H), 6.53(s, 2H), 6.85 (d, J=8.14 Hz, 2H), 7.18 (m, 5H), 7.51 (m, 1H), 7.59 (m,1H)

Example 831

¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (d, J=6.44 Hz, 3H), 0.79 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.91 (d, J=6.78 Hz, 3H), 1.87 (m, 1H),2.09 (m, 1H), 2.75 (dd, J=14.07, 10.68 Hz, 1H), 2.91 (m, 2H), 3.08 (dd,J=14.07, 4.24 Hz, 1H), 3.15 (m, 2H), 3.50 (d, J=17.97 Hz, 1H), 3.74 (m,1H), 3.93 (s, 3H), 3.97 (d, J=10.85 Hz, 1H), 4.10 (s, 1H), 4.30 (m, 1H),4.45 (s, 2H), 4.94 (m, 2H), 6.49 (d, J=9.16 Hz, 1H), 7.04 (dd, J=8.31,2.20 Hz, 1H), 7.13 (m, 7H), 7.35 (d, J=8.48 Hz, 1H), 7.90 (dd, J=7.97,1.53 Hz, 1H), 8.36 (dd, J=4.92, 1.53 Hz, 1H)

Example 832

¹H NMR (300 MHz, CDCl₃) δ ppm 0.75 (d, J=6.78 Hz, 3H), 0.81 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.94 (t, J=6.44 Hz, 3H), 1.80 (dd,J=14.58, 7.80 Hz, 2H), 2.05 (m, 1H), 2.29 (s, 3H), 2.64 (dd, J=14.07,10.68 Hz, 1H), 2.77 (m, 1H), 3.04 (m, 1H), 3.18 (m, 2H), 3.53 (d,J=17.97 Hz, 1H), 3.78 (m, 1H), 3.85 (d, J=10.85 Hz, 1H), 4.21 (q, J=7.12Hz, 1H), 4.52 (m, 2H), 5.93 (m, 2H), 6.07 (d, J=9.49 Hz, 1H), 6.76 (d,J=8.14 Hz, 1H), 6.87 (d, J=8.48 Hz, 1H), 6.91 (m, 2H), 7.03 (m, 5H),7.50 (dd, J=8.48, 2.37 Hz, 1H), 7.55 (d, J=2.03 Hz, 1H), 8.02 (s, 2H)

Example 833

¹H NMR (300 MHz, CD₃OD) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.83 (d, J=6.44Hz, 3H), 0.86 (d, J=6.44 Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 2.01 (m, 2H),2.50 (dd, J=13.73, 11.70 Hz, 1H), 2.86 (dd, J=13.56, 6.78 Hz, 1H), 2.99(m, 2H), 3.11 (d, J=17.97 Hz, 1H), 3.22 (dd, J=13.90, 3.39 Hz, 1H), 3.38(dd, J=14.92, 3.73 Hz, 1H), 3.78 (m, 2H), 3.96 (s, 3H), 4.02 (d, J=10.85Hz, 1H), 4.16 (m, 1H), 4.97 (m, 2H), 6.90 (m, 2H), 7.00 (m, 3H), 7.16(m, 2H), 7.24 (m, 1H), 7.31 (m, 1H), 7.52 (d, J=7.80 Hz, 1H), 7.59 (d,J=7.46 Hz, 1H), 7.65 (m, 2H), 7.89 (s, 1H)

Example 834

¹H NMR (300 MHz, CDCl₃) δ ppm 0.83 (m, 6H), 0.88 (d, J=6.78 Hz, 3H),0.95 (d, J=6.44 Hz, 3H), 1.80 (s, 1H), 2.10 (s, 1H), 2.30 (s, 3H), 2.73(dd, J=14.24, 10.51 Hz, 1H), 2.80 (m, 1H), 2.95 (d, J=4.41 Hz, 3H), 3.02(m, 2H), 3.17 (m, 1H), 3.39 (d, J=17.63 Hz, 1H), 3.69 (d, J=17.97 Hz,1H), 3.83 (s, 1H), 3.87 (d, J=10.85 Hz, 1H), 4.16 (d, J=14.92 Hz, 1H),4.80 (s, 2H), 6.13 (s, 1H), 6.63 (s, 1H), 6.89 (m, 1H), 6.98 (s, 1H),7.04 (s, 1H), 7.14 (s, 5H), 7.50 (dd, J=8.48, 2.03 Hz, 1H), 7.55 (d,J=2.03 Hz, 2H)

Example 835

¹H NMR (300 MHz, CDCl₃) δ ppm 0.78 (d, J=6.44 Hz, 6H), 0.90 (d, J=6.44Hz, 6H), 1.86 (s, 2H), 2.12 (s, 2H), 2.30 (s, 3H), 2.60 (s, 3H), 2.85(m, 2H), 3.07 (m, 3H), 3.38 (d, J=17.97 Hz, 1H), 3.66 (d, J=18.31 Hz,1H), 3.86 (s, 2H), 4.17 (m, 1H), 4.69 (s, 2H), 6.46 (s, 1H), 6.94 (m,1H), 7.12 (s, 6H), 7.34 (s, 1H), 7.44 (d, J=7.12 Hz, 1H), 7.49 (s, 1H)

Example 836

¹H NMR (300 MHz, CDCl₃) δ ppm 0.70 (d, J=6.44 Hz, 3H), 0.75 (d, J=6.44Hz, 3H), 0.91 (m, 6H), 1.90 (m, 2H), 2.08 (m, 2H), 2.24 (s, 3H), 2.79(m, 1H), 3.07 (m, 2H), 3.57 (d, J=18.31 Hz, 1H), 3.70 (m, 1H), 4.12 (m,1H), 4.18 (d, J=10.51 Hz, 1H), 4.27 (t, J=10.17 Hz, 1H), 4.74 (s, 2H),6.83 (s, 1H), 7.05 (dd, J=8.31, 2.20 Hz, 3H), 7.11 (m, 5H), 7.22 (m,2H), 7.37 (m, 1H), 8.02 (s, 1H)

Example 837

¹H NMR (300 MHz, CDCl₃) δ ppm 0.70 (d, J=6.44 Hz, 3H), 0.75 (d, J=6.44Hz, 3H), 0.88 (d, J=6.78 Hz, 3H), 0.91 (m, 3H), 1.90 (m, 2H), 2.08 (m,2H), 2.24 (s, 3H), 2.78 (m, 2H), 3.04 (m, 2H), 3.11 (m, 1H), 3.63 (m,2H), 4.12 (m, 1H), 4.18 (d, J=10.51 Hz, 1H), 4.27 (t, J=10.17 Hz, 1H),4.74 (s, 2H), 6.83 (s, 1H), 7.05 (dd, J=8.31, 2.20 Hz, 2H), 7.11 (m,6H), 7.22 (m, 2H), 7.37 (m, 1H), 8.02 (s, 1H)

Example 838

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.87 (m, 6H),0.94 (d, J=6.44 Hz, 3H), 1.81 (d, J=6.78 Hz, 2H), 2.06 (m, 1H), 2.30 (d,J=3.05 Hz, 3H), 2.71 (m, 1H), 2.79 (m, 1H), 3.07 (m, 1H), 3.19 (m, 1H),3.40 (d, J=17.97 Hz, 1H), 3.65 (d, J=17.97 Hz, 1H), 3.87 (m, 2H), 4.29(d, J=18.31 Hz, 2H), 4.62 (m, 2H), 6.14 (d, J=9.16 Hz, 1H), 6.87 (d,J=8.48 Hz, 1H), 7.11 (m, 3H), 7.22 (m, 2H), 7.48 (m, 2H), 7.58 (m, 1H),7.66 (s, 1H), 8.02 (s, 1H), 8.68 (d, J=4.75 Hz, 1H)

Example 839

¹H NMR (300 MHz, CDCl₃) δ ppm 0.80 (d, J=6.78 Hz, 3H), 0.83 (d, J=6.78Hz, 3H), 0.88 (d, J=6.44 Hz, 3H), 0.95 (d, J=6.44 Hz, 3H), 1.83 (s, 1H),2.09 (d, J=10.51 Hz, 1H), 2.30 (d, J=3.73 Hz, 4H), 2.70 (s, 3H), 2.79(dd, J=13.56, 6.44 Hz, 1H), 3.02 (m, 2H), 3.19 (m, 1H), 3.33 (d, J=17.97Hz, 1H), 3.64 (d, J=17.97 Hz, 1H), 3.86 (m, 2H), 4.32 (d, J=17.63 Hz,1H), 4.68 (m, 2H), 5.71 (s, 1H), 6.13 (d, J=9.16 Hz, 1H), 6.86 (d,J=8.48 Hz, 1H), 7.10 (m, 5H), 7.23 (m, 2H), 7.41 (m, 1H), 7.54 (m, 1H),7.56 (m, 1H), 7.96 (m, 1H), 8.02 (s, 1H)

Example 840

¹H NMR (300 MHz, CDCl₃) δ ppm 0.77 (d, J=6.78 Hz, 3H), 0.80 (d, J=6.78Hz, 3H), 0.89 (d, J=6.78 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.83 (m, 1H),2.07 (m, 1H), 2.62 (dd, J=14.07, 10.68 Hz, 1H), 2.83 (dd, J=13.39, 6.95Hz, 1H), 2.91 (d, J=13.22 Hz, 1H), 3.01 (m, 2H), 3.17 (m, 1H), 3.56 (d,J=17.97 Hz, 1H), 3.66 (s, 1H), 3.83 (s, 1H), 3.89 (d, J=10.51 Hz, 1H),4.20 (m, 1H), 4.41 (s, 1H), 4.63 (s, 2H), 4.69 (s, 2H), 6.27 (d, J=9.83Hz, 1H), 7.01 (m, 2H), 7.06 (m, 5H), 7.16 (d, J=2.03 Hz, 1H), 7.24 (s,1H), 7.29 (d, J=5.09 Hz, 1H), 7.33 (m, 2H), 7.36 (d, J=8.48 Hz, 1H),7.43 (s, 1H)

Example 841

¹H NMR (300 MHz, CDCl₃) δ ppm 0.65 (d, J=6.44 Hz, 3H), 0.81 (m, 3H),0.88 (d, J=6.44 Hz, 3H), 0.92 (m, 3H), 1.23 (m, 2H), 1.89 (m, 2H), 2.21(s, 3H), 2.75 (m, 1H), 2.81 (m, 1H), 2.95 (m, 2H), 3.05 (m, 2H), 3.11(m, 1H), 3.67 (s, 2H), 4.12 (q, J=7.35 Hz, 1H), 4.25 (m, 2H), 4.53 (s,1H), 4.70 (m, 2H), 6.80 (s, 1H), 6.93 (s, 1H), 7.04 (m, 1H), 7.12 (m,5H), 7.21 (d, J=2.03 Hz, 1H), 7.38 (m, 1H)

Example 842

¹H NMR (300 MHz, CDCl₃) δ ppm 0.74 (d, J=6.44 Hz, 3H), 0.86 (m, 6H),0.92 (d, J=6.44 Hz, 3H), 1.01 (m, 1H), 1.37 (m, 1H), 1.83 (m, 1H), 1.93(d, J=16.95 Hz, 1H), 2.70 (dd, J=14.07, 10.68 Hz, 1H), 2.83 (dd,J=13.22, 6.78 Hz, 1H), 2.90 (d, J=8.48 Hz, 1H), 2.96 (m, 1H), 3.05 (m,1H), 3.42 (d, J=17.97 Hz, 1H), 3.70 (d, J=17.63 Hz, 1H), 3.77 (d, J=2.71Hz, 1H), 3.87 (m, 3H), 4.04 (m, 1H), 4.24 (m, 1H), 4.42 (s, 2H), 4.90(m, 2H), 6.31 (d, J=9.16 Hz, 1H), 6.85 (t, J=2.71 Hz, 1H), 7.03 (dd,J=8.48, 2.03 Hz, 1H), 7.08 (dd, J=8.99, 2.54 Hz, 1H), 7.14 (m, 5H), 7.17(d, J=2.03 Hz, 1H), 7.20 (m, 1H), 7.35 (d, J=8.14 Hz, 1H), 7.75 (m, 1H),7.85 (m, 1H)

Example 843

¹H NMR (300 MHz, CDCl₃) δ ppm 0.79 (d, J=6.44 Hz, 3H), 0.84 (m, 3H),0.88 (d, J=6.44 Hz, 3H), 0.93 (d, J=6.78 Hz, 3H), 1.22 (m, 1H), 1.86 (m,2H), 2.68 (dd, J=14.24, 10.85 Hz, 1H), 2.82 (dd, J=13.22, 6.78 Hz, 1H),3.02 (m, 3H), 3.18 (m, 1H), 3.40 (m, 1H), 3.63 (d, J=17.97 Hz, 2H), 3.84(m, 1H), 4.00 (d, J=10.85 Hz, 1H), 4.27 (m, 1H), 4.39 (s, 2H), 5.08 (m,2H), 6.16 (d, J=9.49 Hz, 1H), 7.06 (m, 7H), 7.17 (m, 1H), 7.36 (m, 2H),7.64 (m, 1H), 7.76 (m, 1 H), 8.15 (d, J=7.46 Hz, 1H), 8.28 (d, J=7.46Hz, 1H), 8.88 (d, J=4.41 Hz, 1H)

Example 844

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.70 (m, 6H), 0.85 (m, 1H), 1.17 (t,J=7.12 Hz, 4H), 1.24 (d, J=3.05 Hz, 1H), 1.50 (m, 6H), 1.94 (m, 1H),2.23 (s, 1H), 2.36 (m, 1H), 2.59 (s, 3H), 2.73 (s, 1H), 2.88 (d, J=6.78Hz, 1H), 2.95 (m, 1H), 3.03 (m, 1H), 3.09 (m, 1H), 3.19 (m, 2H), 3.31(m, 1H), 3.76 (d, J=17.97 Hz, 1H), 3.90 (s, 1H), 4.01 (m, 1H), 4.64 (s,2H), 6.99 (m, 3H), 7.07 (m, 2H), 7.24 (s, 1H), 7.79 (s, 2H), 7.95 (m,3H), 8.24 (d, J=9.49 Hz, 1H), 8.85 (s, 1H)

The foregoing is merely illustrative of the invention and is notintended to limit the invention to the disclosed compounds. Variationsand changes which are obvious to one skilled in the art are intended tobe within the scoped of the nature of the invention which are defined inthe appended claims.

1. A compound of formula (I),

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein: Ais R₅C(O)—, R₆SO₂—,

X is O, S or NH; Y is O, S or NH; R is alkyl, alkenyl, cycloalkyl,cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, arylalkyl orheteroarylalkyl; wherein each R is substituted with 0, 1, or 2substituents selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, halo, formyl, nitro, hydroxy, alkoxy, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, haloalkyl, hydroxyalkyl andalkoxyalkyl; R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a); R₂ is H;R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₅ is alkyl, haloalkyl,cyanoalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, —OalkylSO₂alkyl,—O-heterocycle, -alkyl-O-aryl or —O-alkyl-heteroaryl; wherein theheterocycle, aryl or heteroaryl moiety of —O-heterocycle, -alkyl-O-aryland —O-alkyl-heteroaryl is independently substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of cyano,halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂; R₆ isaryl or heteroaryl; wherein each R₆ is substituted with 0 or 1substituent selected from the group consisting of —C(H)═NOH,—C(alkyl)=NOH, —C(H)═NO(alkyl), —C(alkyl)=NO(alkyl), —C(H)═NO(arylalkyl)and —C(alkyl)=NO(arylalkyl); R₇ is hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇ issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₈ is—C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b), R_(8a) and R_(8b) are, ateach occurrence, independently selected from the group consisting ofalkyl, arylalkyl and heteroarylalkyl; wherein each R_(8a) and R_(8b) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of alkyl, nitro,hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl; R₉ is alkyl, alkenyl, alkynyl,—C(═O)NR_(a)R_(b), —C(═O)OR_(a), cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle; wherein each R₉ is substituted with 0, 1, 2or 3 substituents independently selected from the group consisting ofalkyl, alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(9a); R_(9a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(9a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R₁₀ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b),—C(═O)OR_(a), cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle;wherein each R₁₀ is substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(10a); R_(10a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(10a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R₁₁ is alkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b),—C(═O)OR_(a), cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle;wherein each R₁₁ is substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(11a); R_(11a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(11a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl), —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R₁₂ is alkyl, alkenyl, cycloalkyl, cycloalkenyl,cycloalkylalkyl or cycloalkenylalkyl; wherein each R₁₂ is substitutedwith 0, 1 or 2 substituents independently selected from the groupconsisting of hydroxy, alkoxy cyano, nitro and halo; R₁₃ is alkyl,alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl orheterocycle; wherein each R₁₃ is substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, halo, nitro, oxo, —OR_(a), —OC(═O)R_(a),—SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b),—N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(13a); R_(13a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(13a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R_(a) and R_(b) at each occurrence areindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; whereineach R_(a) and R_(b), at each occurrence, is independently substitutedwith 0, 1, 2 or 3 substituents independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo,hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl),—SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); alternatively,R_(a) and R_(b), together with the nitrogen atom they are attached, forma heterocycle ring substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) -alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or
 2. 2-6. (canceled)
 7. The compound of claim 1 having formula(II)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein Ris alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl,cycloalkenylalkyl, arylalkyl or heteroarylalkyl; wherein each R issubstituted with 0, 1, or 2 substituents selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl, nitro,hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,haloalkyl, hydroxyalkyl and alkoxyalkyl; R₁ is OR_(a), —OSO₂R_(a),—OSO₃R_(a), —OPO₃R_(a), —OC(═O)C(H)(R_(1a))NR_(a)R_(b) or—OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a); R_(1a) is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl orheteroarylalkyl; wherein each R_(1a) is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b)and —C(═O)OR_(a); R₂ is H; R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl,alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl,cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl,heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylNR_(a)R_(b), -alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₇ is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇is substituted with 0, 1 or 2 substituents independently selected fromthe group consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₈ is—C(═O)OR_(8a) or —C(═O)alkylNR_(8a)R_(8b), R_(8a) and R_(8b) are, ateach occurrence, independently selected from the group consisting ofalkyl, arylalkyl and heteroarylalkyl; wherein each R_(8a) and R_(8b) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of alkyl, nitro,hydroxy, alkoxy, amino, formyl, halo, haloalkyl, hydroxyalkyl,alkoxyalky aminoalkyl and formylalkyl; R_(a) and R_(b) at eachoccurrence are independently selected from the group consisting ofhydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl orheterocycle; wherein each R_(a) and R_(b), at each occurrence, isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of alkyl, alkenyl, alkynyl, cyano,formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); and R_(c) is aryl, heteroaryl orheterocycle; wherein each R_(c) is independently substituted with 0, 1,2, 3 or 4 substituents independently selected from the group consistingof halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.8-13. (canceled)
 14. The compound of claim 1 having formula (III)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein Xis O, S or NH; R is alkyl, alkenyl, cycloalkyl, cycloalkenyl,cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl;wherein each R is substituted with 0, 1, or 2 substituents selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl,nitro, hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R₁ is OR_(a),—OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a), —OC(═O)C(H)(R_(1a))NR_(a)R_(b) or—OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a); R_(1a) is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl orheteroarylalkyl; wherein each R_(1a) is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b)and —C(═O)OR_(a); R₂ is H; R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl,alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl,cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl,heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylNR_(a)R_(b), -alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₇ is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇is substituted with 0, 1 or 2 substituents independently selected fromthe group consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₉ isalkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a), cycloalkyl,cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R₉ issubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro,oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a),—SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(9a); R_(9a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(9a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R_(a) and R_(b) at each occurrence areindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; whereineach R_(a) and R_(b), at each occurrence, is independently substitutedwith 0, 1, 2 or 3 substituents independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo,hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl),—SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); alternatively,R_(a) and R_(b), together with the nitrogen atom they are attached, forma heterocycle ring substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) -alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or
 2. 15. The compound of claim 14 wherein R₁ is OH and R₂ is H.16. The compound of claim 14 wherein R₁ is OH, R₂ is H, X is O and R₃ isalkyl, cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl,heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a) or -alkylNR_(a)R_(b).
 17. The compound ofclaim 14 wherein R₁ is OH, R₂ is H, X is O, R₃ is alkyl or cycloalkyland R₄ is aryl or heteroaryl.
 18. The compound of claim 14 wherein R₁ isOH, R₂ is H, X is O, R₃ is alkyl or cycloalkylalkyl and R₄ is phenyl.19. The compound of claim 14 wherein R₁ is OH, R₂ is H, X is O, R₃ isalkyl or cycloalkylalkyl and R₄ is phenyl substituted with 0, 1, 2, 3 or4 substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.20. The compound of claim 14 wherein R₁ is OH, R₂ is H, X is O, R₃ isalkyl or cycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.
 21. (canceled)
 22. The compound of claim 1 havingformula (IV)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein Xis O, S or NH; R is alkyl, alkenyl, cycloalkyl, cycloalkenyl,cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl;wherein each R is substituted with 0, 1, or 2 substituents selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formylnitro, hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R₁ is OR_(a),—OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a), —OC(═O)C(H)(R_(1a))NR_(a)R_(b) or—OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a); R_(1a) is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl orheteroarylalkyl; wherein each R_(1a) is substituted with 0, 1 or 2substituents independently selected from the group consisting of halo,alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a), —N(R_(b))SO₂NR_(a)R_(b),—N(R_(b))C(═NH)NR_(a)R_(b), —N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b)and —C(═O)OR_(a); R₂ is H; R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl,alkynyl, haloalkynyl, cycloalkyl, cycloalkenyl, cycloalkenylalkyl,cycloalkylalkyl, heterocycle, heterocyclealkyl, heteroaryl,heteroarylalkyl, aryl, arylalkyl, hydroxyalkyl, alkoxyalkyl,haloalkoxyalkyl, -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylNR_(a)R_(b), -alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₇ is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇is substituted with 0, 1 or 2 substituents independently selected fromthe group consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₁₀ isalkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a), cycloalkyl,cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R₁₀ issubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro,oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a),—SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(10a); R_(10a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(10a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R_(a) and R_(b) at each occurrence areindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; whereineach R_(a) and R_(b), at each occurrence, is independently substitutedwith 0, 1, 2 or 3 substituents independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo,hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl),—SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); alternatively,R_(a) and R_(b), together with the nitrogen atom they are attached, forma heterocycle ring substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) -alkylC(═O)N(alkyl)₂ and R_(c);and R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.23-28. (canceled)
 29. The compound of claim 1 having formula (V)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein Xis O, S or NH; Y is O, S or NH; R is alkyl, alkenyl, cycloalkyl,cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, arylalkyl orheteroarylalkyl; wherein each R is substituted with 0, 1, or 2substituents selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, halo, formyl, nitro, hydroxy, alkoxy, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, haloalkyl, hydroxyalkyl andalkoxyalkyl; R₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a); R₂ is H;R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH,—C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₇ is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇is substituted with 0, 1 or 2 substituents independently selected fromthe group consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₁₁ isalkyl, alkenyl, alkynyl, —C(═O)NR_(a)R_(b), —C(═O)OR_(a), cycloalkyl,cycloalkenyl, aryl, heteroaryl or heterocycle; wherein each R₁₁ issubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, nitro,oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a), —SO₂NR_(a),—SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b), —N(R_(b))C(═O)R_(a),—N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))C(═O)NR_(a)R_(b),—N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a), —C(═O)NR_(a)R_(b), —C(═O)OR_(a),azidoalkyl, haloalkyl, nitroalkyl, cyanoalkyl, -alkylOR_(a),-alkylOC(═O)R_(a), -alkylSR_(a), -alkylSOR_(a), -alkylSO₂R_(a),-alkylSO₂NR_(a), -alkylSO₂OR_(a), -alkylNR_(a)R_(b), —C(H)═N(OR_(a)),—C(alkyl)=N(OR_(a)), —C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b),—C(H)(═NOR_(a))NR_(a)R_(b), —C(alkyl)(═NOR_(a))NR_(a)R_(b),-alkylN(R_(b))NR_(a)R_(b), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)NR_(a)R_(b),-alkylN(R_(b))SO₂NR_(a)R_(b), -alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a),-alkylC(═O)OR_(a), -alkylC(═O)NR_(a)R_(b) and R_(11a); R_(11a) iscycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl; wherein eachR_(11a) is substituted with 0, 1, 2, 3 or 4 substituents independentlyselected from the group consisting of cyano, halo, nitro, oxo, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH,—S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl,formylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and-alkylC(═O)N(alkyl)₂; R_(a) and R_(b) at each occurrence areindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocycle; whereineach R_(a) and R_(b), at each occurrence, is independently substitutedwith 0, 1, 2 or 3 substituents independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo,hydroxy, alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl),—SO₂(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂,-alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); alternatively,R_(a) and R_(b), together with the nitrogen atom they are attached, forma heterocycle ring substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) -alkylC(═O)N(alkyl)₂ and R_(c);R_(c) is aryl, heteroaryl or heterocycle; wherein each R_(c) isindependently substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of halo, nitro, oxo,alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; andn is 1 or
 2. 30. The compound of claim 29 wherein R₁ is OH and R₂ is H.31. The compound of claim 29 wherein R₁ is OH, R₂ is H, X is O, Y is Oand R₃ is alkyl, cycloalkenylalkyl, cycloalkylalkyl, heterocyclealkyl,heteroarylalkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a) or -alkylNR_(a)R_(b).
 32. The compound ofclaim 29 wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkyl and R₄ is aryl or heteroaryl.
 33. The compound of claim 29wherein R₁ is OH, R₂ is H, X is O, Y is O, R₃ is alkyl orcycloalkylalkyl and R₄ is phenyl substituted with 0, 1, 2, 3 or 4substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a); wherein R_(4a) and R_(4b) areindependently selected from the group consisting of hydrogen and alkyl.34. The compound of claim 29 wherein R₁ is OH, R₂ is H, X is O, Y is O,R₃ is alkyl or cycloalkylalkyl, R₄ is phenyl substituted with 0, 1, 2, 3or 4 substituents selected from the group consisting of halo, —OR_(4a),—NR_(4a)R_(4b) and —C(R_(4b))═NOR_(4a), and R₇ is alkyl; wherein R_(4a)and R_(4b) are independently selected from the group consisting ofhydrogen and alkyl.
 35. (canceled)
 36. The compound of claim 1 havingformula (VI)

or a pharmaceutically acceptable salt form, stereoisomer, ester, salt ofan ester, prodrug, salt of a prodrug, or combination thereof, wherein Xis O, S or NH; R is alkyl, alkenyl, cycloalkyl, cycloalkenyl,cycloalkylalkyl, cycloalkenylalkyl, arylalkyl or heteroarylalkyl;wherein each R is substituted with 0, 1, or 2 substituents selected fromthe group consisting of alkyl, alkenyl, alkynyl, cyano, halo, formyl,nitro, hydroxy, alkoxy, —NH₂, —N(H)alkyl, —N(alkyl)₂, —C(═O)OH,—C(═O)Oalkyl, haloalkyl, hydroxyalkyl and alkoxyalkyl; R₁ is H and R₂ isOR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a); orR₁ is OR_(a), —OSO₂R_(a), —OSO₃R_(a), —OPO₃R_(a),—OC(═O)C(H)(R_(1a))NR_(a)R_(b) or —OC(═O)C(H)(R_(1a))N(H)C(O)OR_(a);R_(1a) is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aryl, arylalkyl, heteroaryl or heteroarylalkyl; wherein each R_(1a) issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halo, alkyl, alkenyl, alkynyl, —OR_(a), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(a))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b) and —C(═O)OR_(a); R₂ is H;R₃ is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl,cycloalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkyl,heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, aryl,arylalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylNR_(a)R_(b),-alkylN(R_(b))C(═O)OR_(a), -alkylN(R_(b))C(═O)R_(a),-alkylN(R_(b))SO₂R_(a) or -alkylN(R_(b))SO₂NR_(a)R_(b); wherein each ofthe cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylmoiety of the cycloalkylalkyl, cycloalkenyl moiety of thecycloalkenylalkyl, hetrocycle moiety of the heterocyclealkyl, heteroarylmoiety of the heteroarylalkyl, aryl moiety of the arylalkyl isindependently substituted with 0, 1, 2 or 3 substituents independentlyselected from the group consisting of halo, nitro, cyano, formyl, alkyl,alkenyl, alkynyl, hydroxy, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl)₂, —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl,—C(═O)OH, —C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂,-alkylC(═O)alkyl and R_(3a); R_(3a) is cycloalkyl, cycloalkenyl, aryl,heteroaryl or heterocycle, wherein each R_(3a) is independentlysubstituted with 0, 1, 2 or 3 substituents independently selected fromthe group consisting of halo, nitro, cyano, formyl, alkyl, alkenyl,alkynyl, hydroxyl, alkoxy, —SH, —S(alkyl), —SO₂(alkyl), —NH₂,—N(H)(alkyl), —N(alkyl), —N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —C(═O)OH,—C(═O)O(alkyl), —C(═O)NH₂, —C(═O)N(H)(alkyl), —C(O)N(alkyl)₂,—C(═O)alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl,formylalkyl, nitroalkyl, -alkylSH, -alkylS(alkyl), -alkylSO₂(alkyl),-alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)alkyl,-alkylN(alkyl)C(═O)alkyl, -alkylC(═O)OH, -alkylC(═O)O(alkyl),-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl), -alkylC(═O)N(alkyl)₂ and-alkylC(═O)alkyl; R₄ is cycloalkyl, cycloalkenyl, heterocycle, aryl orheteroaryl wherein each R₄ is substituted with 0, 1, 2, 3 or 4substituents independently selected from the group consisting of halo,alkyl, oxo, alkenyl, alkynyl, nitro, cyano, haloalkyl, cyanoalkyl,hydroxyalkyl, alkoxyalkyl, nitroalkyl, —OR_(4a), —SR_(4a), —SOR_(4a),—SO₂R_(4a), —NR_(4a)R_(4b), —OC(═O)R_(4a), —C(═O)R_(4a), —C(═O)OR_(4a),—C(═O)NR_(4a)R_(4b), —N(R_(4b))C(═O)R_(4a), —N(R_(4b))C(═O)OR_(4a),—N(R_(4b))SO₂R_(4a), —N(R_(4b))C(═O)NR_(4a)R_(4b),—N(R_(4b))SO₂NR_(4a)R_(4b), -alkylSR_(4a), -alkylSOR_(4a),-alkylSO₂R_(4a), -alkylNR_(4a)R_(4b), -alkylOC(═O)R_(4a),-alkylC(═O)R_(4a), -alkylC(═O)OR_(4a), -alkylC(═O)NR_(4a)R_(4b),-alkylN(R_(4b))C(═O)R_(4a), -alkylN(R_(4b))C(═O)OR_(4a),-alkylN(R_(4b))SO₂R_(4a), -alkylN(R_(4b))C(═O)NR_(4a)R_(4b),-alkylN(R_(4b))SO₂NR_(4a)R_(4b), —N(H)C(═O)alkylN(H)C(═O)OR_(4a),—N(H)C(═O)alkylNR_(4a)R_(4b), —C(R_(4b))═NOR_(4a),—C(NR_(4a)R_(4b))═NOR_(4a) and —C(R_(4b))═NOC(═O)alkylNR_(4a)R_(4b);R_(4a) and R_(4b), at each occurrence, are independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, aryl, arylalkyl, heterocycle, heterocyclealkyl,heteroaryl and heteroalkyl; wherein each R_(4a) and R_(4b), at eachoccurrence, is independently substituted with 0, 1 or 2 substituentsindependently selected from the group consisting of alkyl, alkenyl,hydroxy, alkoxy, halo, nitro, cyano, formyl, oxo, —NH₂, —N(H)alkyl,—N(alkyl)₂, —C(═O)alkyl, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)alkyl, —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl, cyanoalkyl,nitroalkyl, formylalkyl and alkoxyalkyl; R₇ is hydrogen, alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, aryl or heteroaryl; wherein each R₇is substituted with 0, 1 or 2 substituents independently selected fromthe group consisting of halo, —OR_(a), —OalkylC(═O)NR_(a)R_(b), —SR_(a),—SOR_(a), —SO₂R_(a), —SO₂NR_(a)R_(b), —C(═O)R_(a), —NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))C(═O)OR_(a), —N(R_(b))SO₂R_(a),—N(R_(b))SO₂NR_(a)R_(b), —N(R_(b))C(═NH)NR_(a)R_(b),—N(R_(b))C(═O)NR_(a)R_(b), —C(═O)NR_(a)R_(b), —C(═O)OR_(a) and R_(7a);R_(7a) is cycloalkyl, cycloalkenyl, heterocycle, aryl or heteroaryl;wherein each R_(7a) is substituted with 0, 1, 2, 3 or 4 substituentsindependently selected from the group consisting of cyano, halo, nitro,oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂, —N(H)(alkyl),—N(alkyl), —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl), -alkylN(alkyl)₂,-alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂; R₁₂ isalkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl orcycloalkenylalkyl; wherein each R₁₂ is substituted with 0, 1 or 2substituents independently selected from the group consisting ofhydroxy, alkoxy cyano, nitro and halo; R₁₃ is alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle; wherein eachR₁₃ is substituted with 0, 1, 2 or 3 substituents independently selectedfrom the group consisting of alkyl, alkenyl, alkynyl, cyano, halo,nitro, oxo, —OR_(a), —OC(═O)R_(a), —SR_(a), —SOR_(a), —SO₂R_(a),—SO₂NR_(a), —SO₂OR_(a), —NR_(a)R_(b), —N(R_(b))NR_(a)R_(b),—N(R_(b))C(═O)R_(a), —N(R_(b))SO₂R_(a), —N(R_(b))C(═O)OR_(a),—N(R_(b))C(═O)NR_(a)R_(b), —N(R_(b))SO₂NR_(a)R_(b), —C(═O)R_(a),—C(═O)NR_(a)R_(b), —C(═O)OR_(a), azidoalkyl, haloalkyl, nitroalkyl,cyanoalkyl, -alkylOR_(a), -alkylOC(═O)R_(a), -alkylSR_(a),-alkylSOR_(a), -alkylSO₂R_(a), -alkylSO₂NR_(a), -alkylSO₂OR_(a),-alkylNR_(a)R_(b), —C(H)═N(OR_(a)), —C(alkyl)=N(OR_(a)),—C(H)═NNR_(a)R_(b), —C(alkyl)=NNR_(a)R_(b), —C(H)(═NOR_(a))NR_(a)R_(b),—C(alkyl)(═NOR_(a))NR_(a)R_(b), -alkylN(R_(b))NR_(a)R_(b),-alkylN(R_(b))C(═O)R_(a), -alkylN(R_(b))C(═O)OR_(a),-alkylN(R_(b))C(═O)NR_(a)R_(b), -alkylN(R_(b))SO₂NR_(a)R_(b),-alkylN(R_(b))SO₂R_(a), -alkylC(═O)R_(a), -alkylC(═O)OR_(a),-alkylC(═O)NR_(a)R_(b) and R_(13a); R_(13a) is cycloalkyl, cycloalkenyl,heterocycle, aryl or heteroaryl; wherein each R_(13a) is substitutedwith 0, 1, 2, 3 or 4 substituents independently selected from the groupconsisting of cyano, halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy,alkoxy, —NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl) and -alkylC(═O)N(alkyl)₂; R_(a)and R_(b) at each occurrence are independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heteroaryl or heterocycle; wherein each R_(a) and R_(b), at eachoccurrence, is independently substituted with 0, 1, 2 or 3 substituentsindependently selected from the group consisting of alkyl, alkenyl,alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl, nitroalkyl,haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂, -alkylN(H)(alkyl),-alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂, -alkylN(H)C(═O)N(H)(alkyl),-alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH, -alkylC(═O)Oalkyl,-alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c);alternatively, R_(a) and R_(b), together with the nitrogen atom they areattached, form a heterocycle ring substituted with 0, 1, 2 or 3substituents independently selected from the group consisting of alkyl,alkenyl, alkynyl, cyano, formyl, nitro, halo, oxo, hydroxy, alkoxy,—NH₂, —N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl),—N(H)C(═O)alkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂,—N(H)C(═O)N(H)(alkyl), —N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C(═O)Oalkyl,—C(═O)NH₂, —C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, cyanoalkyl, formylalkyl,nitroalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylNH₂,-alkylN(H)(alkyl), -alkylN(alkyl)₂, -alkylN(H)C(═O)NH₂,-alkylN(H)C(═O)N(H)(alkyl), -alkylN(H)C(═O)N(alkyl)₂, -alkylC(═O)OH,-alkylC(═O)Oalkyl, -alkylC(═O)NH₂, -alkylC(═O)N(H)(alkyl)-alkylC(═O)N(alkyl)₂ and R_(c); and R_(c) is aryl, heteroaryl orheterocycle; wherein each R_(c) is independently substituted with 0, 1,2, 3 or 4 substituents independently selected from the group consistingof halo, nitro, oxo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, —NH₂,—N(H)(alkyl), —N(alkyl)₂, —SH, —S(alkyl), —SO₂(alkyl), —N(H)C(═O)alkyl,—N(alkyl)C(═O)alkyl, —N(H)C(═O)NH₂, —N(H)C(═O)N(H)(alkyl),—N(H)C(═O)N(alkyl)₂, —C(═O)OH, —C═O)Oalkyl, —C(═O)NH₂,—C(═O)N(H)(alkyl), —C(═O)N(alkyl)₂, haloalkyl, hydroxyalkyl,alkoxyalkyl, -alkylNH₂, -alkyl-N(H)(alkyl), -alkyl-N(alkyl)₂,-alkyl-N(H)C(═O)NH₂, -alkyl-N(H)C(═O)N(H)(alkyl),-alkyl-N(H)C(═O)N(alkyl)₂, -alkyl-C(═O)OH, -alkyl-C(═O)Oalkyl,-alkyl-C(═O)NH₂, -alkyl-C(═O)N(H)(alkyl) and -alkyl-C(═O)N(alkyl)₂.37-42. (canceled)
 43. A pharmaceutical composition comprising atherapeutically effective amount of a compound or combination ofcompounds of claim 1, and a pharmaceutically acceptable carrier. 44-49.(canceled)
 50. A method of inhibiting the replication of an HIV viruscomprising contacting said virus with a therapeutically effective amountof a compound or combination of compounds of claim
 1. 51. A method oftreating or preventing an HIV infection comprising administering to apatient in need of such treatment a therapeutically effective amount ofa compound or combination of compounds of claim
 1. 52-53. (canceled)